Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Thymus as Incontrovertible Target of Future Immune Modulatory Therapeutics

Author(s): Ghulam Jilany Khan*, Abeeha Imtiaz, Wei Wang, Hong Duan, Hui Cao, Kefeng Zhai and Nongyue He*

Volume 24, Issue 14, 2024

Published on: 12 February, 2024

Page: [1586 - 1610] Pages: 25

DOI: 10.2174/0118715303283164240126104109

Price: $65

Abstract

Thymus plays a crucial role in cellular immunity by acting as a warehouse for proliferating and differentiating lymphocytes. Thymic stromal cells educate T-cells to differentiate self from non-self antigens while nurse cells and thymoproteasome play a major role in the maturation and differentiation of T-cells. The thymic conditions dictate T-cells to cope with the risk of cancer development. A study was designed to demonstrate potential mechanisms behind the failure to eliminate tumors and impaired immune surveillance as well as the impact of delay in thymus regression on cancer and autoimmune disorders. Scientific literature from Pubmed; Scopus; WOS; JSTOR; National Library of Medicine Bethesda, Maryland; The New York Academy of Medicine; Library of Speech Rehabilitation, NY; St. Thomas’ Hospital Library; The Wills Library of Guys Hospital; Repository of Kings College London; and Oxford Academic repository was explored for pathological, physiological, immunological and toxicological studies of thymus. Studies have shown that systemic chemotherapy may lead to micro inflammatory environment within thymus where conventionally and dynamically metastasized dormant cells seek refuge. The malfunctioning of the thymus and defective T and Treg cells, bypassing negative selection, contributes to autoimmune disorders, while AIRE and Fezf2 play significant roles in thymic epithelial cell solidity. Different vitamins, TCM, and live cell therapy are effective therapeutics. Vitamin A, C, D, and E, selenium and zinc, cinobufagin and dietary polysaccharides, and glandular extracts and live cell injections have strong potential to restore immune system function and thymus health. Moreover, the relationship between different ages/ stages of thymus and their corresponding T-cell mediated anti-tumor immune response needs further exploration.

Next »
[1]
Brayton, H.W. Heublein, Enlarged thymus gland in infancy and its treatment by radium. Boston. Med. Surg. J., 1919, 181, 740-743.
[http://dx.doi.org/10.1056/NEJM191912251812604]
[2]
Miller, J.F.A.P. Thymus and immunity-II. The last three decades. Eur. J. Cancer Clin. Oncol., 1988, 24(8), 1257-1262.
[http://dx.doi.org/10.1016/0277-5379(88)90212-X]
[3]
Henry, G.L.R.S. A Greek-English Lexicon. 2023. Available from: http://www.perseus.tufts.edu/hopper/text?doc=Perseus:text:1999.04.0057:entry=qhri/on
[4]
Omnia, C.G.O. Galeni in Hippocrat. de alimento. In: Cambridge Library Collection - Classics. Vol. Classics; Kühn, K., Ed.; Cambridge University Press: Cambridge, 2011.
[5]
Omnia, C.G.O. De tumoribus praeter naturam. In: Cambridge Library Collection Classics; Kühn, K., Ed.; Cambridge University Press, 2011.
[6]
Totelin, L. Hippocratic Corpus; Oxford University Press, 2021.
[7]
Kowalski, G. De corporis humani partium appellationibus; Hrsg. von Georg, Kowalski, Ed.; , 1960.
[8]
Lavini, C. Thymus gland pathology: clinical, diagnostic and therapeutic features; Springer Science & Business Media, 2009.
[9]
Platter, F.; Plater, F. Observations, on the majority of man's affections, on the body and mind, on the injury of the functions, on pain, on other discomforts, and insensible vices, three books ... Now the second time of the order to be typed ... to the autograph in many places amended, Medicines not described in the work ... richer; Impensis Ludovici König: Basileae 1641, 912.
[10]
Platter, F.; Brandmuller, J.; Konig, J.L. Observationum Felicis Plateri ... three books with as many practical treatises of his character & corresponding method, and the emotions of the body & narrating graphically the histories of many souls, both faithfully and diligently observed, and the treatments successfully performed; The third time is now the type of commandment, and in addition to the anakephaliosin of drugs, & a list of the most fruitful things, in the second edition, added; purged of innumerable wrongs, which had been omitted in the previous two. New, moreover, Fel. Plater, Fel. from Fr. niece Mantissa selections of observations, enriched; typis & impensis Joh. Ludovici König & Johannis Brandmylleri.: Basileae 1680.
[11]
Hewson, W. The Works of William Hewson, FRS; Sydenham Society, 1846, Vol. 7, .
[http://dx.doi.org/10.5962/bhl.title.23264]
[12]
Doyle, D. William Hewson (1739–74): The father of haematology. Br. J. Haematol., 2006, 133(4), 375-381.
[13]
Silverman, F.J.R. In search of lost time and the thymus (with apologies to Marcel Proust). Radiology, 1993, 186(2), 310-311.
[14]
Astley, C. The anatomy of the thymus gland. ed. R. Longman, Orme, Green, and Brown; Longman, Rees, Orme, Green, and Brown; 1832.: Wellcome Collection.: 183 Euston Road, London NW1 2BE UK London, 1832.
[15]
Simon, J. A physiological essay on the thymus gland. London Henry Renshaw MDCCCXLV 1845.
[http://dx.doi.org/10.5962/bhl.title.106561]
[16]
Hassall, A.H. A physiological essay on the thymus gland. Med. Chir. Rev., 1855, 2(3), 18-35.
[17]
Hammar, J.A. The new views at the morphology of the thymus gland and their hearing on the problem of the function of the thymus. Endocrinology, 1921, 5(5), 543-573.
[18]
Hammar, J.A. The new views as to the morphology of the thymus gland and their bearing on the problem of the function of the thymus. Endocrinology., 1921, 5(5), 543-573.
[http://dx.doi.org/10.1210/endo-5-5-543]
[19]
Selye, H. The general adaptation syndrome and the diseases of adaptation. J. Clin. Endocrinol. Metab., 1946, 6(2), 117-230.
[http://dx.doi.org/10.1210/jcem-6-2-117]
[20]
Selye, H. The Stress in health and disease; Pacifica Tape Library; New York: McGraw-Hill, 1976.
[21]
Miller, J. Immunological function of the thymus. Lancet, 1961, 278(7205), 748-749.
[http://dx.doi.org/10.1016/S0140-6736(61)90693-6]
[22]
Miller, J.F.; Osoba, D. Current concepts of the immunological function of the thymus. Physiol. Rev., 1967, 47(3), 437-520.
[http://dx.doi.org/10.1152/physrev.1967.47.3.437]
[23]
Palmer, S.; Albergante, L.; Blackburn, C.C.; Newman, T.J. Thymic involution and rising disease incidence with age. Proc. Natl. Acad. Sci., 2018, 115(8), 1883-1888.
[http://dx.doi.org/10.1073/pnas.1714478115]
[24]
Andreasen, E.; Christensen, S. The rate of mitotic activity in the lymphoid organs of the rat. Anat. Rec., 1949, 103(3), 401-412.
[http://dx.doi.org/10.1002/ar.1091030307]
[25]
Nakamura, K.; Metcalf, D. Quantitative cytological studies on thymic lymphoid cells in normal, preleukaemic and leukaemic mice. Br. J. Cancer, 1961, 15(2), 306-315.
[http://dx.doi.org/10.1038/bjc.1961.38]
[26]
Thapa, P.; Farber, D.L. The role of the thymus in the immune response. Thorac. Surg. Clin., 2019, 29(2), 123-131.
[http://dx.doi.org/10.1016/j.thorsurg.2018.12.001]
[27]
Steinmann, G.; Klaus, B.; Müller‐Hermelink, H.K.J.S.j.o.i. The involution of the ageing human thymic epithelium is independent of puberty: A morphometric study. 1985, 22(5), 563-575.
[http://dx.doi.org/10.1111/j.1365-3083.1985.tb01916.x]
[28]
Bajoghli, B.; Guo, P.; Aghaallaei, N.; Hirano, M.; Strohmeier, C.; McCurley, N.; Bockman, D.E.; Schorpp, M.; Cooper, M.D.; Boehm, T. A thymus candidate in lampreys. Nature, 2011, 470(7332), 90-94.
[http://dx.doi.org/10.1038/nature09655]
[29]
Litman, G.W.; Rast, J.P.; Fugmann, S.D. The origins of vertebrate adaptive immunity. Nat. Rev. Immunol., 2010, 10(8), 543-553.
[http://dx.doi.org/10.1038/nri2807]
[30]
Pancer, Z.; Cooper, M.D. The evolution of adaptive immunity. Annu. Rev. Immunol., 2006, 24(1), 497-518.
[http://dx.doi.org/10.1146/annurev.immunol.24.021605.090542]
[31]
Gorgollon, P. Fine structure of the thymus in the adult cling fish Sicyases sanguineus (Pisces, Gobiesocidae). J. Morphol., 1983, 177(1), 25-40.
[http://dx.doi.org/10.1002/jmor.1051770103]
[32]
Parrott, D.M.; East, J.J.P.R.S.M. The thymus and immnity [abridged] the immunological status of thymectomized animals—. Survey, 1964, 57(2), 147-151.
[33]
Gowans, J.L. McGREGOR, D.D.; Cowen, D.M.; Ford, C.E. Initiation of immune responses by small lymphocytes. Nature, 1962, 196(4855), 651-655.
[http://dx.doi.org/10.1038/196651a0]
[34]
Medawar, P.B. The croonian lecture: The homograft reaction. Proc. Royal Soc. B, 1958, 149(935), 145-166.
[35]
Miller, J.F.A.P. Immunity in the foetus and the new-born. Br. Med. Bull., 1966, 22(1), 21-26.
[http://dx.doi.org/10.1093/oxfordjournals.bmb.a070431]
[36]
Kennedy, J.C. A transplantation assay for mouse cells responsive to antigenic stimulation by sheep erythrocytes. Proc. Soc. Exp. Biol. Med., 1965, 120(3), 868-873.
[http://dx.doi.org/10.3181/00379727-120-30678]
[37]
Adams, G.B.; Chabner, K.T.; Foxall, R.B.; Weibrecht, K.W.; Rodrigues, N.P.; Dombkowski, D.; Fallon, R.; Poznansky, M.C.; Scadden, D.T. Heterologous cells cooperate to augment stem cell migration, homing, and engraftment. Blood, 2003, 101(1), 45-51.
[http://dx.doi.org/10.1182/blood-2002-02-0486]
[38]
Vos, O. Transplantation of homologous and heterologous lymphoid cells in x-irradiated and non-irradiated mice. J. Natl. Cancer Inst., 1959, 23(1), 53-73.
[39]
Miller, J.F.A.P.; Haddow, A. Effect of neonatal thymectomy on the immunological responsiveness of the mouse. Proc. R. Soc. Lond. B., 1962, 156(964), 415-428.
[40]
Miller, J.F.A.P. Analysis of the thymus influence in leukæmogenesis. Nature, 1961, 191(4785), 248-249.
[http://dx.doi.org/10.1038/191248a0]
[41]
Miller, J.F.A.P.; Sprent, J. Thymus-derived cells in mouse thoracic duct lymph. Nat. New Biol., 1971, 230(17), 267-271.
[http://dx.doi.org/10.1038/newbio230267a0]
[42]
Moore, M.A.S.; Owen, J.J.T. Stem-cell migration in developing myeloid and lymphoid systems. Lancet, 1967, 290(7517), 658-659.
[http://dx.doi.org/10.1016/S0140-6736(67)90693-9]
[43]
Hofman, L.; Stanković, V.; Allegretti, N.; Stankovic, V.; Allegretti, N. The effect of total-body x-irradiation on the thymus and the number of its cells. Radiat. Res., 1961, 15(1), 30-38.
[http://dx.doi.org/10.2307/3571064]
[44]
Miller, J.F.A.P. Immunological significance of the thymus of the adult mouse. Nature, 1962, 195(4848), 1318-1319.
[http://dx.doi.org/10.1038/1951318a0]
[45]
Cross, A.M.; Leuchars, E.; Miller, J.F.A.P. Studies on the recovery of the immune response in irradiated mice thymectomized in adult life. J. Exp. Med., 1964, 119(5), 837-850.
[http://dx.doi.org/10.1084/jem.119.5.837]
[46]
Miller, J.F.A.P. Effect of thymectomy in adult mice on immunological responsiveness. Nature, 1965, 208(5017), 1337-1338.
[http://dx.doi.org/10.1038/2081337a0]
[47]
Sperling, B. Thymoma: A review of the clinical and pathological findings in 65 cases. Can. J. Surg., 2003, 46(1), 37-42.
[48]
Den Bakker, M.A.; Oosterhuis, J.W. Tumours and tumour-like conditions of the thymus other than thymoma; a practical approach. Histopathology, 2009, 54(1), 69-89.
[http://dx.doi.org/10.1111/j.1365-2559.2008.03177.x]
[49]
Miller, J.F.A.P.; Grant, G.A.; Roe, F.J.C. Effect of thymectomy on the induction of skin tumours by 3,4-benzopyrene. Nature, 1963, 199(4896), 920-922.
[http://dx.doi.org/10.1038/199920a0]
[50]
Grant, G.A.; Miller, J.F.A.P. Effect of neonatal thymectomy on the induction of sarcomata in C57BL mice. Nature, 1965, 205(4976), 1124-1125.
[http://dx.doi.org/10.1038/2051124a0]
[51]
Miller, J.F.A.P.; Ting, R.C.; Law, L.W. Influence of thymectomy on tumor induction by polyoma virus in C57BL mice. Proc. Soc. Exp. Biol. Med., 1964, 116, 323-327.
[http://dx.doi.org/10.3181/00379727-116-29237]
[52]
Fichtelius, K.E.; Laurell, G.; Philipsson, L. The influence of thymectomy on antibody formation. Acta Pathol. Microbiol. Scand., 1961, 51(2), 81-86.
[http://dx.doi.org/10.1111/j.1699-0463.1961.tb00346.x]
[53]
Martinez, C.; Kersey, J.; Papermaster, B.W.; Good, R.A. Skin homograft survival in thymectomized mice. Exp. Biol. Med., 1962, 109(1), 193-196.
[http://dx.doi.org/10.3181/00379727-109-27149]
[54]
Dalmasso, A. Further studies of suppression of the homograft reaction by thymectomy in the mouse. Proc. Soc. Exp. Biol. Med., 1962, 111(1), 143-146.
[http://dx.doi.org/10.3181/00379727-111-27729]
[55]
Arnason, B.G.; Janković, B.D.; Waksman, B.H.J.N. Effect of thymectomy on ‘delayed’hypersensitive reactions. Nature, 1962, 194(4823), 99-100.
[56]
McIntire, K.; Sell, S.; Miller, J.J.N. Pathogenesis of the post-neonatal thymectomy wasting syndrome. Nature, 1964, 204, 151-155.
[http://dx.doi.org/10.1038/204151a0]
[57]
Warner, N.J.A.J.o.E.B.; Science, M. The immunological role of different lymphoid organs in the chicken: ii. The immunological competence of thymic cell suspensions. Aust. J. Exp. Biol. Med. Sci., 1964, 42, 401-416.
[http://dx.doi.org/10.1038/icb.1964.38]
[58]
Claman, H.N.; Chaperon, E.A.; Triplett, R.F. Thymus-marrow cell combinations. Synergism in antibody production. Exp. Biol. Med., 1966, 122(4), 1167-1171.
[http://dx.doi.org/10.3181/00379727-122-31353]
[59]
Miller, J.F. The croonian lecture, 1992. The key role of the thymus in the body’s defence strategies. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1992, 337(1279), 105-124.
[http://dx.doi.org/10.1098/rstb.1992.0087]
[60]
Durgeau, A.; Virk, Y.; Corgnac, S.; Mami-Chouaib, F. Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy. Front. Immunol., 2018, 9, 14.
[http://dx.doi.org/10.3389/fimmu.2018.00014]
[61]
Kunzmann, V.; Bauer, E.; Feurle, J.; Tony, F.W.H-P.; Wilhelm, M. Stimulation of γδ T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood, 2000, 96(2), 384-392.
[http://dx.doi.org/10.1182/blood.V96.2.384.013k07_384_392]
[62]
Minetto, P.; Guolo, F.; Pesce, S.; Greppi, M.; Obino, V.; Ferretti, E.; Sivori, S.; Genova, C.; Lemoli, R.M.; Marcenaro, E. Harnessing NK cells for cancer treatment. Front. Immunol., 2019, 10, 2836.
[http://dx.doi.org/10.3389/fimmu.2019.02836]
[63]
Godfrey, D.I.; Koay, H-F.; McCluskey, J.; Gherardin, N.A. The biology and functional importance of MAIT cells. Nat. Immunol., 2019, 20(9), 1110-1128.
[http://dx.doi.org/10.1038/s41590-019-0444-8]
[64]
Eisel, D.; Das, K.; Dickes, E.; König, R.; Osen, W.; Eichmüller, S.B. Cognate interaction with CD4+ T cells instructs tumor-associated macrophages to acquire M1-like phenotype. Front. Immunol., 2019, 10, 219.
[http://dx.doi.org/10.3389/fimmu.2019.00219]
[65]
Farhood, B.; Najafi, M.; Mortezaee, K. CD8 + cytotoxic T lymphocytes in cancer immunotherapy: A review. J. Cell. Physiol., 2019, 234(6), 8509-8521.
[http://dx.doi.org/10.1002/jcp.27782]
[66]
Dunn, G.P.; Old, L.J.; Schreiber, R.D. The immunobiology of cancer immunosurveillance and immunoediting. Immunity, 2004, 21(2), 137-148.
[http://dx.doi.org/10.1016/j.immuni.2004.07.017]
[67]
Kreslavsky, T.; Gleimer, M.; von Boehmer, H. αβ versus γδ lineage choice at the first TCR-controlled checkpoint. Curr. Opin. Immunol., 2010, 22(2), 185-192.
[http://dx.doi.org/10.1016/j.coi.2009.12.006]
[68]
Sambandam, A.; Maillard, I.; Zediak, V.P.; Xu, L.; Gerstein, R.M.; Aster, J.C.; Pear, W.S.; Bhandoola, A. Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat. Immunol., 2005, 6(7), 663-670.
[http://dx.doi.org/10.1038/ni1216]
[69]
Rothenberg, E.V. Programming for T-lymphocyte fates: Modularity and mechanisms. Genes Dev., 2019, 33(17-18), 1117-1135.
[http://dx.doi.org/10.1101/gad.327163.119]
[70]
Boudil, A.; Matei, I.R.; Shih, H-Y.; Bogdanoski, G.; Yuan, J.S.; Chang, S.G.; Montpellier, B.; Kowalski, P.E.; Voisin, V.; Bashir, S.; Bader, G.D.; Krangel, M.S.; Guidos, C.J. IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection. Nat. Immunol., 2015, 16(4), 397-405.
[http://dx.doi.org/10.1038/ni.3122]
[71]
Koch, U.; Radtke, F. Mechanisms of T cell development and transformation. Annu. Rev. Cell Dev. Biol., 2011, 27(1), 539-562.
[http://dx.doi.org/10.1146/annurev-cellbio-092910-154008]
[72]
Colombo, M.P.; Piconese, S. Regulatory T-cell inhibition versus depletion: The right choice in cancer immunotherapy. Nat. Rev. Cancer, 2007, 7(11), 880-887.
[http://dx.doi.org/10.1038/nrc2250]
[73]
Klein, L.; Robey, E.A.; Hsieh, C.S. Central CD4+ T cell tolerance: Deletion versus regulatory T cell differentiation. Nat. Rev. Immunol., 2019, 19(1), 7-18.
[http://dx.doi.org/10.1038/s41577-018-0083-6]
[74]
Kisielow, P.; Blüthmann, H.; Staerz, U.D.; Steinmetz, M.; von Boehmer, H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature, 1988, 333(6175), 742-746.
[http://dx.doi.org/10.1038/333742a0]
[75]
Kappler, J.W.; Roehm, N.; Marrack, P. T cell tolerance by clonal elimination in the thymus. Cell, 1987, 49(2), 273-280.
[http://dx.doi.org/10.1016/0092-8674(87)90568-X]
[76]
Ohki, H.; Martin, C.; Corbel, C.; Coltey, M.; Le Douarin, N.M. Tolerance induced by thymic epithelial grafts in birds. Science, 1987, 237(4818), 1032-1035.
[http://dx.doi.org/10.1126/science.3616623]
[77]
Scollay, R.G.; Butcher, E.C.; Weissman, I.L. Thymus cell migration: Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur. J. Immunol., 1980, 10(3), 210-218.
[http://dx.doi.org/10.1002/eji.1830100310]
[78]
Sur, D.; Banu, S. Role of macrophage in type 2 diabetes mellitus: Macrophage polarization a new paradigm for treatment of type 2 diabetes mellitus. Endocr. Metab. Immune Disord. Drug Targets, 2023, 23(1), 2-11.
[http://dx.doi.org/10.2174/1871530322666220630093359]
[79]
Doshi, G.M.; Ansari, A.Z.; Bhatia, N.Y.; Gharat, S.A.; Godad, A.P. Exploring cytokines as potential target in peptic ulcer disease: A systematic update. Endocr. Metab. Immune Disord. Drug Targets, 2023, 23(1), 21-34.
[http://dx.doi.org/10.2174/1871530322666220829142124]
[80]
Sakaguchi, S.; Sakaguchi, N.; Asano, M.; Itoh, M.; Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol., 1995, 155(3), 1151-1164.
[http://dx.doi.org/10.4049/jimmunol.155.3.1151]
[81]
Ott, I.; Scott, J.C. The action of glandular extracts upon the contractions of the uterus. J. Exp. Med., 1909, 11(2), 326-330.
[http://dx.doi.org/10.1084/jem.11.2.326]
[82]
du Vigneaud, V.; Ressler, C.; Trippett, S. The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. J. Biol. Chem., 1953, 205(2), 949-957.
[http://dx.doi.org/10.1016/S0021-9258(18)49238-1]
[83]
Geenen, V.; Legros, J-J.; Franchimont, P.; Baudrihaye, M.; Defresne, M-P.; Boniver, J. The neuroendocrine thymus: Coexistence of oxytocin and neurophysin in the human thymus. Science, 1986, 232(4749), 508-511.
[http://dx.doi.org/10.1126/science.3961493]
[84]
Geenen, V.; Legros, J-J.; Franchimont, P.; Defresne, M-P.; Boniver, J.; Ivell, R.; Richter, D. The thymus as a neuroendocrine organ. Synthesis of vasopressin and oxytocin in human thymic epithelium. Ann. N. Y. Acad. Sci., 1987, 496(1), 56-66.
[http://dx.doi.org/10.1111/j.1749-6632.1987.tb35746.x]
[85]
Geenen, V.; Defresne, M-P.; Robert, F.; Legros, J-J.; Franchimont, P.; Boniver, J. The neurohormonal thymic microenvironment: Immunocytochemical evidence that thymic nurse cells are neuroendocrine cells. Neuroendocrinology, 1988, 47(4), 365-368.
[http://dx.doi.org/10.1159/000124938]
[86]
Nakagawa, Y.; Ohigashi, I.; Nitta, T.; Sakata, M.; Tanaka, K.; Murata, S.; Kanagawa, O.; Takahama, Y. Thymic nurse cells provide microenvironment for secondary T cell receptor α rearrangement in cortical thymocytes. Proc. Natl. Acad. Sci., 2012, 109(50), 20572-20577.
[http://dx.doi.org/10.1073/pnas.1213069109]
[87]
Marilda, M.; Rosa, L.; Stefano, T.; Marta, B.; Alfonsina, C.; Fiammetta, N.; Giulia, P.; Marialuisa, A. Syndrome of inappropriate antidiuresis and diabetes insipidus as two sides of the same coin in hypothalamic lymphoma: A case report. Endocr. Metab. Immune Disord. Drug Targets, 2023, 23(5), 732-737.
[http://dx.doi.org/10.2174/1871530323666221124125253]
[88]
Geenen, V.; Bodart, G.; Henry, S.; Michaux, H.; Dardenne, O.; Charlet-Renard, C.; Martens, H.; Hober, D. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity. Front. Neurosci., 2013, 7, 187.
[http://dx.doi.org/10.3389/fnins.2013.00187]
[89]
Hale, J.S.; Boursalian, T.E.; Turk, G.L.; Fink, P.J. Thymic output in aged mice. Proc. Natl. Acad. Sci., 2006, 103(22), 8447-8452.
[http://dx.doi.org/10.1073/pnas.0601040103]
[90]
Petrie, H.T. Role of thymic organ structure and stromal composition in steady‐state postnatal T‐cell production. Immunol. Rev., 2002, 189(1), 8-20.
[http://dx.doi.org/10.1034/j.1600-065X.2002.18902.x]
[91]
Esmaeilzadeh, H.; Rezaei, N.; Aminorroaya, A.; Rayzan, E.; Shahkarami, S.; Seyedpour, S.; Zoghi, S.; Aryan, Z.; Somekh, I.; Rohlfs, M.; Klein, C. Novel DNMT3B mutation in a patient with immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome and a bronchopulmonary collateral artery. Endocr. Metab. Immune Disord. Drug Targets, 2023, 23(3), 410-415.
[http://dx.doi.org/10.2174/1871530322666220822141722]
[92]
Hinterberger, M.; Aichinger, M.; Prazeres da Costa, O.; Voehringer, D.; Hoffmann, R.; Klein, L. Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance. Nat. Immunol., 2010, 11(6), 512-519.
[http://dx.doi.org/10.1038/ni.1874]
[93]
Oh, J.; Wang, W.; Thomas, R.; Su, D-M. Capacity of tTreg generation is not impaired in the atrophied thymus. PLoS Biol., 2017, 15(11), e2003352.
[http://dx.doi.org/10.1371/journal.pbio.2003352]
[94]
Khan, I.S.; Mouchess, M.L.; Zhu, M-L.; Conley, B.; Fasano, K.J.; Hou, Y.; Fong, L.; Su, M.A.; Anderson, M.S. Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance. J. Exp. Med., 2014, 211(5), 761-768.
[http://dx.doi.org/10.1084/jem.20131889]
[95]
Su, M.A.; Anderson, M.S. Breaking through the central tolerance ceiling to unleash anticancer immune responses. OncoImmunology, 2014, 3(8), e950169.
[http://dx.doi.org/10.4161/21624011.2014.950169]
[96]
Chaudhary, R.; Gupta, S.; Chauhan, S. Protein uncoupling as an innovative practice in diabetes mellitus treatment: A metabolic disorder. Endocr. Metab. Immune Disord. Drug Targets, 2023, 23(4), 494-502.
[http://dx.doi.org/10.2174/1871530322666220902143401]
[97]
Chougnet, C.A.; Tripathi, P.; Lages, C.S.; Raynor, J.; Sholl, A.; Fink, P.; Plas, D.R.; Hildeman, D.A. A major role for Bim in regulatory T cell homeostasis. J. Immunol., 2011, 186(1), 156-163.
[http://dx.doi.org/10.4049/jimmunol.1001505]
[98]
White, M.C.; Holman, D.M.; Boehm, J.E.; Peipins, L.A.; Grossman, M.; Jane Henley, S. Age and cancer risk: A potentially modifiable relationship. Am. J. Prev. Med., 2014, 46(3), S7-S15.
[http://dx.doi.org/10.1016/j.amepre.2013.10.029]
[99]
Takeuchi, Y.; Nishikawa, H. Roles of regulatory T cells in cancer immunity. Int. Immunol., 2016, 28(8), 401-409.
[http://dx.doi.org/10.1093/intimm/dxw025]
[100]
Tanaka, A.; Sakaguchi, S. Regulatory T cells in cancer immunotherapy. Cell Res., 2017, 27(1), 109-118.
[http://dx.doi.org/10.1038/cr.2016.151]
[101]
Ohm, J.E.; Gabrilovich, D.I.; Sempowski, G.D.; Kisseleva, E.; Parman, K.S.; Nadaf, S.; Carbone, D.P. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood, 2003, 101(12), 4878-4886.
[http://dx.doi.org/10.1182/blood-2002-07-1956]
[102]
Mandal, D.; Bhattacharyya, A.; Lahiry, L.; Choudhuri, T.; Sa, G.; Das, T. Failure in peripheral immuno-surveillance due to thymic atrophy: Importance of thymocyte maturation and apoptosis in adult tumor-bearer. Life Sci., 2005, 77(21), 2703-2716.
[http://dx.doi.org/10.1016/j.lfs.2005.05.038]
[103]
Sizova, O.; Kuriatnikov, D.; Liu, Y.; Su, D-M. Atrophied thymus, a tumor reservoir for harboring melanoma cells. Mol. Cancer Res., 2018, 16(11), 1652-1664.
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0308]
[104]
Bent, E.H.; Gilbert, L.A.; Hemann, M.T. A senescence secretory switch mediated by PI3K/AKT/mTOR activation controls chemoprotective endothelial secretory responses. Genes Dev., 2016, 30(16), 1811-1821.
[http://dx.doi.org/10.1101/gad.284851.116]
[105]
Thomas, R.; Wang, W.; Su, D.M. Contributions of age-related thymic involution to immunosenescence and inflammaging. Immun. Ageing, 2020, 17(1), 2.
[http://dx.doi.org/10.1186/s12979-020-0173-8]
[106]
Pawelec, G. Age and immunity: What is “immunosenescence”? Exp. Gerontol., 2018, 105, 4-9.
[http://dx.doi.org/10.1016/j.exger.2017.10.024]
[107]
Hurez, V.; Padrón, Á.; Svatek, R.S.; Curiel, T.J. Considerations for successful cancer immunotherapy in aged hosts. Exp. Gerontol., 2018, 107, 27-36.
[http://dx.doi.org/10.1016/j.exger.2017.10.002]
[108]
Pawelec, G. Does patient age influence anti-cancer immunity? Semin. Immunopathol., 2019, 41(1), 125-131.
[http://dx.doi.org/10.1007/s00281-018-0697-6]
[109]
Bayegi, S.N.; Hamidieh, A.A.; Behfar, M.; Saghazadeh, A.; Bozorgmehr, M.; Tajik, N.; Delbandi, A.A.; Delavari, S.; Shekarabi, M.; Rezaei, N. The reconstitution of T-cells after allogeneic hematopoietic stem cell transplant in a pediatric patient with congenital amegakaryocytic thrombocytopenia (CAMT). Endocr. Metab. Immune Disord. Drug Targets, 2024, 24(2), 265-272.
[http://dx.doi.org/10.2174/1871530323666230801100113]
[110]
Fukushima, Y.; Minato, N.; Hattori, M. The impact of senescence-associated T cells on immunosenescence and age-related disorders. Inflamm. Regen., 2018, 38(1), 24.
[http://dx.doi.org/10.1186/s41232-018-0082-9]
[111]
Coulie, P.G.; Van den Eynde, B.J.; van der Bruggen, P.; Boon, T. Tumour antigens recognized by T lymphocytes: At the core of cancer immunotherapy. Nat. Rev. Cancer, 2014, 14(2), 135-146.
[http://dx.doi.org/10.1038/nrc3670]
[112]
Zhang, H.; Liu, L.; Zhang, J.; Chen, J.; Ye, J.; Shukla, S.; Qiao, J.; Zhan, X.; Chen, H.; Wu, C.J.; Fu, Y-X.; Li, B. Investigation of antigen-specific t-cell receptor clusters in human cancers. Clin. Cancer Res., 2020, 26(6), 1359-1371.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-3249]
[113]
Schreiber, K.; Karrison, T.G.; Wolf, S.P.; Kiyotani, K.; Steiner, M.; Littmann, E.R.; Pamer, E.G.; Kammertoens, T.; Schreiber, H.; Leisegang, M. Impact of TCR diversity on the development of transplanted or chemically induced tumors. Cancer Immunol. Res., 2020, 8(2), 192-202.
[http://dx.doi.org/10.1158/2326-6066.CIR-19-0567]
[114]
Vallejo, A.N. CD28 extinction in human T cells: Altered functions and the program of T‐cell senescence. Immunol. Rev., 2005, 205(1), 158-169.
[http://dx.doi.org/10.1111/j.0105-2896.2005.00256.x]
[115]
Shimatani, K.; Nakashima, Y.; Hattori, M.; Hamazaki, Y.; Minato, N. PD-1 + memory phenotype CD4 + T cells expressing C/EBPα underlie T cell immunodepression in senescence and leukemia. Proc. Natl. Acad. Sci., 2009, 106(37), 15807-15812.
[http://dx.doi.org/10.1073/pnas.0908805106]
[116]
Sato, K.; Kato, A.; Sekai, M.; Hamazaki, Y.; Minato, N. Physiologic thymic involution underlies age-dependent accumulation of senescence-associated CD4+ T cells. J. Immunol., 2017, 199(1), 138-148.
[http://dx.doi.org/10.4049/jimmunol.1602005]
[117]
Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12(4), 252-264.
[http://dx.doi.org/10.1038/nrc3239]
[118]
Minato, N.; Hattori, M.; Hamazaki, Y. Physiology and pathology of T-cell aging. Int. Immunol., 2020, 32(4), 223-231.
[http://dx.doi.org/10.1093/intimm/dxaa006]
[119]
Ribot, J.C.; Lopes, N.; Silva-Santos, B. γδ T cells in tissue physiology and surveillance. Nat. Rev. Immunol., 2021, 21(4), 221-232.
[http://dx.doi.org/10.1038/s41577-020-00452-4]
[120]
Jesenak, M. Successful treatment of severe allergic asthma with omalizumab in a girl with DiGeorge syndrome. Cent. Eur. J. Immunol., 2020, 45(3), 361-363.
[http://dx.doi.org/10.5114/ceji.2020.101269]
[121]
Chakraverty, R.; Teshima, T. Graft-versus-host disease: A disorder of tissue regeneration and repair. Blood, 2021, 138(18), 1657-1665.
[http://dx.doi.org/10.1182/blood.2021011867]
[122]
Strange, C.D.; Ahuja, J.; Shroff, G.S.; Truong, M.T.; Marom, E.M. Imaging evaluation of thymoma and thymic carcinoma. Front. Oncol., 2022, 11, 810419.
[http://dx.doi.org/10.3389/fonc.2021.810419]
[123]
Blum, T.G.; Misch, D.; Kollmeier, J.; Thiel, S.; Bauer, T.T. Autoimmune disorders and paraneoplastic syndromes in thymoma. J. Thorac. Dis., 2020, 12(12), 7571-7590.
[http://dx.doi.org/10.21037/jtd-2019-thym-10]
[124]
Shelly, S.; Agmon-Levin, N.; Altman, A.; Shoenfeld, Y. Thymoma and autoimmunity. Cell. Mol. Immunol., 2011, 8(3), 199-202.
[http://dx.doi.org/10.1038/cmi.2010.74]
[125]
Ibis, B.; Konstantinos, A.; Carol, C.; Sasitorn, Y.; Vassiliki, A.B. Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases. Front. Immunol., 2023, 14, 1197364.
[http://dx.doi.org/10.3389/fimmu.2023.1197364]
[126]
Chang, A.; Nataraja, R.M.; Pudel, E.; Stunden, R.; Baré, S.; Pacilli, M. Diagnosis and management of ectopic cervical thymus in children: Systematic review of the literature. J. Pediatr. Surg., 2021, 56(11), 2062-2068.
[http://dx.doi.org/10.1016/j.jpedsurg.2021.03.003]
[127]
Khan, G.J.; Sun, L.; Abbas, M.; Naveed, M.; Jamshaid, T.; Baig, M.M.F.A.; Yuan, S. In vitro pre-treatment of cancer cells with TGF-β1: A novel approach of tail vein lung cancer metastasis mouse model for anti-metastatic studies. Curr. Mol. Pharmacol., 2019, 12(4), 249-260.
[http://dx.doi.org/10.2174/1874467212666190306165703]
[128]
Khan, G.J.; Sun, L.; Khan, S.; Yuan, S.; Nongyue, H. Versatility of cancer associated fibroblasts: Commendable targets for anti-tumor therapy. Curr. Drug Targets, 2018, 19(13), 1573-1588.
[http://dx.doi.org/10.2174/1389450119666180219124439]
[129]
Pantel, K.; Alix-Panabières, C. Circulating tumour cells in cancer patients: Challenges and perspectives. Trends Mol. Med., 2010, 16(9), 398-406.
[http://dx.doi.org/10.1016/j.molmed.2010.07.001]
[130]
Bakhshi, M.S.; Rizwan, M.; Khan, G.J.; Duan, H.; Zhai, K. Design of a novel integrated microfluidic chip for continuous separation of circulating tumor cells from peripheral blood cells. Sci. Rep., 2022, 12(1), 17016.
[http://dx.doi.org/10.1038/s41598-022-20886-1]
[131]
Marlow, R.; Honeth, G.; Lombardi, S.; Cariati, M.; Hessey, S.; Pipili, A.; Mariotti, V.; Buchupalli, B.; Foster, K.; Bonnet, D.; Grigoriadis, A.; Rameshwar, P.; Purushotham, A.; Tutt, A.; Dontu, G. A novel model of dormancy for bone metastatic breast cancer cells. Cancer Res., 2013, 73(23), 6886-6899.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0991]
[132]
Wang, X.; Hassan, W.; Jabeen, Q.; Khan, G.J.; Iqbal, F. Interdependent and independent multidimensional role of tumor microenvironment on hepatocellular carcinoma. Cytokine, 2018, 103, 150-159.
[http://dx.doi.org/10.1016/j.cyto.2017.09.026]
[133]
Du, H.; Huang, Y.; Hou, X.; Yu, X.; Lin, S.; Wei, X.; Li, R.; Khan, G.J.; Yuan, S.; Sun, L. DT-13 inhibits cancer cell migration by regulating NMIIA indirectly in the tumor microenvironment. Oncol. Rep., 2016, 36(2), 721-728.
[http://dx.doi.org/10.3892/or.2016.4890]
[134]
Yumoto, K.; Eber, M.R.; Berry, J.E.; Taichman, R.S.; Shiozawa, Y. Molecular pathways: Niches in metastatic dormancy. Clin. Cancer Res., 2014, 20(13), 3384-3389.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0897]
[135]
Sun, Y.; Campisi, J.; Higano, C.; Beer, T.M.; Porter, P.; Coleman, I.; True, L.; Nelson, P.S. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat. Med., 2012, 18(9), 1359-1368.
[http://dx.doi.org/10.1038/nm.2890]
[136]
Klein, C.A. Framework models of tumor dormancy from patient-derived observations. Curr. Opin. Genet. Dev., 2011, 21(1), 42-49.
[http://dx.doi.org/10.1016/j.gde.2010.10.011]
[137]
Aguirre-Ghiso, J.A. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer, 2007, 7(11), 834-846.
[http://dx.doi.org/10.1038/nrc2256]
[138]
Malchow, S.; Leventhal, D.S.; Savage, P.A. Organ-specific regulatory T cells of thymic origin are expanded in murine prostate tumors. OncoImmunology, 2013, 2(7), e24898.
[http://dx.doi.org/10.4161/onci.24898]
[139]
Bakhru, P.; Zhu, M-L.; Wang, H-H.; Hong, L.K.; Khan, I.; Mouchess, M.; Gulati, A.S.; Starmer, J.; Hou, Y.; Sailer, D.; Lee, S.; Zhao, F.; Kirkwood, J.M.; Moschos, S.; Fong, L.; Anderson, M.S.; Su, M.A. Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity. JCI Insight, 2017, 2(18), e93265.
[http://dx.doi.org/10.1172/jci.insight.93265]
[140]
Träger, U.; Sierro, S.; Djordjevic, G.; Bouzo, B.; Khandwala, S.; Meloni, A.; Mortensen, M.; Simon, A.K. The immune response to melanoma is limited by thymic selection of self-antigens. PLoS One, 2012, 7(4), e35005.
[http://dx.doi.org/10.1371/journal.pone.0035005]
[141]
Derbinski, J. Pillars Article: Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral Self. Nat. Immunol. 2001. 2: 1032-1039. J. Immunol., 2016, 196(7), 2915-2922.
[142]
Derbinski, J.; Schulte, A.; Kyewski, B.; Klein, L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat. Immunol., 2001, 2(11), 1032-1039.
[http://dx.doi.org/10.1038/ni723]
[143]
Su, M.A.; Anderson, M.S. Pulling RANK on cancer: Blocking aire-mediated central tolerance to enhance immunotherapy. Cancer Immunol. Res., 2019, 7(6), 854-859.
[http://dx.doi.org/10.1158/2326-6066.CIR-18-0912]
[144]
Cummings, S.R.; Martin, J.S.; McClung, M.R.; Siris, E.S.; Eastell, R.; Reid, I.R.; Delmas, P.; Zoog, H.B.; Austin, M.; Wang, A.; Kutilek, S.; Adami, S.; Zanchetta, J.; Libanati, C.; Siddhanti, S.; Christiansen, C. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med., 2009, 361(8), 756-765.
[http://dx.doi.org/10.1056/NEJMoa0809493]
[145]
Zhu, M.L.; Nagavalli, A.; Su, M.A. Aire deficiency promotes TRP-1-specific immune rejection of melanoma. Cancer Res., 2013, 73(7), 2104-2116.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3781]
[146]
Alexandropoulos, K.; Danzl, N.M. Thymic epithelial cells: Antigen presenting cells that regulate T cell repertoire and tolerance development. Immunol. Res., 2012, 54(1-3), 177-190.
[http://dx.doi.org/10.1007/s12026-012-8301-y]
[147]
Karimi, S.; Chattopadhyay, S.; Chakraborty, N.G. Manipulation of regulatory T cells and antigen‐specific cytotoxic T lymphocyte‐based tumour immunotherapy. Immunology, 2015, 144(2), 186-196.
[http://dx.doi.org/10.1111/imm.12387]
[148]
Turk, M.J.; Wolchok, J.D.; Guevara-Patino, J.A.; Goldberg, S.M.; Houghton, A.N. Multiple pathways to tumor immunity and concomitant autoimmunity. Immunol. Rev., 2002, 188(1), 122-135.
[http://dx.doi.org/10.1034/j.1600-065X.2002.18811.x]
[149]
Takaba, H.; Morishita, Y.; Tomofuji, Y.; Danks, L.; Nitta, T.; Komatsu, N.; Kodama, T.; Takayanagi, H. Fezf2 orchestrates a thymic program of self-antigen expression for immune tolerance. Cell, 2015, 163(4), 975-987.
[http://dx.doi.org/10.1016/j.cell.2015.10.013]
[150]
Akirav, E.M.; Ruddle, N.H.; Herold, K.C. The role of AIRE in human autoimmune disease. Nat. Rev. Endocrinol., 2011, 7(1), 25-33.
[http://dx.doi.org/10.1038/nrendo.2010.200]
[151]
Franzese, O.; Torino, F.; Fuggetta, M.P.; Aquino, A.; Roselli, M.; Bonmassar, E.; Giuliani, A.; D’Atri, S. Tumor immunotherapy: Drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors. Oncotarget, 2017, 8(25), 41641-41669.
[http://dx.doi.org/10.18632/oncotarget.16335]
[152]
Burnet, F.M. A reassessment of the forbidden clone hypothesis of autoimmune disease. Immunol. Cell Biol., 1972, 50(1), 1-9.
[http://dx.doi.org/10.1038/icb.1972.1]
[153]
Kecha-Kamoun, O.; Achour, I.; Martens, H.; Collette, J.; Lefebvre, P.J.; Greiner, D.L.; Geenen, V. Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes. Diabetes Metab. Res. Rev., 2001, 17(2), 146-152.
[http://dx.doi.org/10.1002/dmrr.182]
[154]
Pugliese, A.; Zeller, M.; Fernandez, A., Jr; Zalcberg, L.J.; Bartlett, R.J.; Ricordi, C.; Pietropaolo, M.; Eisenbarth, G.S.; Bennett, S.T.; Patel, D.D. The insulin gene is transcribed in the human thymus and transcription levels correlate with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat. Genet., 1997, 15(3), 293-297.
[http://dx.doi.org/10.1038/ng0397-293]
[155]
Vafiadis, P.; Bennett, S.T.; Todd, J.A.; Nadeau, J.; Grabs, R.; Goodyer, C.G.; Wickramasinghe, S.; Colle, E.; Polychronakos, C. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nat. Genet., 1997, 15(3), 289-292.
[http://dx.doi.org/10.1038/ng0397-289]
[156]
Noso, S.; Kataoka, K.; Kawabata, Y.; Babaya, N.; Hiromine, Y.; Yamaji, K.; Fujisawa, T.; Aramata, S.; Kudo, T.; Takahashi, S.; Ikegami, H. Insulin transactivator MafA regulates intrathymic expression of insulin and affects susceptibility to type 1 diabetes. Diabetes, 2010, 59(10), 2579-2587.
[http://dx.doi.org/10.2337/db10-0476]
[157]
Murakami, M.; Hosoi, Y.; Negishi, T.; Kamiya, Y.; Miyashita, K.; Yamada, M.; Iriuchijima, T.; Yokoo, H.; Yoshida, I.; Tsushima, Y.; Mori, M. Thymic hyperplasia in patients with Graves’ disease. Identification of thyrotropin receptors in human thymus. J. Clin. Invest., 1996, 98(10), 2228-2234.
[http://dx.doi.org/10.1172/JCI119032]
[158]
Paschke, R.; Geenen, V. Messenger RNA expression for a TSH receptor variant in the thymus of a two-year-old child. J. Mol. Med., 1995, 73(11), 577-580.
[http://dx.doi.org/10.1007/BF00195143]
[159]
Sospedra, M.; Ferrer-Francesch, X.; Domínguez, O.; Juan, M.; Foz-Sala, M.; Pujol-Borrell, R. Transcription of a broad range of self-antigens in human thymus suggests a role for central mechanisms in tolerance toward peripheral antigens. J. Immunol., 1998, 161(11), 5918-5929.
[http://dx.doi.org/10.4049/jimmunol.161.11.5918]
[160]
Colobran, R.; Armengol, M.P.; Faner, R.; Gärtner, M.; Tykocinski, L-O.; Lucas, A.; Ruiz, M.; Juan, M.; Kyewski, B.; Pujol-Borrell, R. Association of an SNP with intrathymic transcription of TSHR and Graves’ disease: A role for defective thymic tolerance. Hum. Mol. Genet., 2011, 20(17), 3415-3423.
[http://dx.doi.org/10.1093/hmg/ddr247]
[161]
Lv, H.; Havari, E.; Pinto, S.; Gottumukkala, R.V.S.R.K.; Cornivelli, L.; Raddassi, K.; Matsui, T.; Rosenzweig, A.; Bronson, R.T.; Smith, R.; Fletcher, A.L.; Turley, S.J.; Wucherpfennig, K.; Kyewski, B.; Lipes, M.A. Impaired thymic tolerance to α-myosin directs autoimmunity to the heart in mice and humans. J. Clin. Invest., 2011, 121(4), 1561-1573.
[http://dx.doi.org/10.1172/JCI44583]
[162]
Handel, A.E.; Irani, S.R.; Holländer, G.A. The role of thymic tolerance in CNS autoimmune disease. Nat. Rev. Neurol., 2018, 14(12), 723-734.
[http://dx.doi.org/10.1038/s41582-018-0095-7]
[163]
Aaltonen, J.; Björses, P.; Perheentupa, J.; Horelli-Kuitunen, N.; Palotie, A.; Peltonen, L.; Lee, Y.S.; Francis, F.; Henning, S.; Thiel, C.; Leharach, H.; Yaspo, M-L. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat. Genet., 1997, 17(4), 399-403.
[http://dx.doi.org/10.1038/ng1297-399]
[164]
Nagamine, K.; Peterson, P.; Scott, H.S.; Kudoh, J.; Minoshima, S.; Heino, M.; Krohn, K.J.E.; Lalioti, M.D.; Mullis, P.E.; Antonarakis, S.E.; Kawasaki, K.; Asakawa, S.; Ito, F.; Shimizu, N. Positional cloning of the APECED gene. Nat. Genet., 1997, 17(4), 393-398.
[http://dx.doi.org/10.1038/ng1297-393]
[165]
Irla, M.; Hugues, S.; Gill, J.; Nitta, T.; Hikosaka, Y.; Williams, I.R.; Hubert, F-X.; Scott, H.S.; Takahama, Y.; Holländer, G.A.; Reith, W. Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity. Immunity, 2008, 29(3), 451-463.
[http://dx.doi.org/10.1016/j.immuni.2008.08.007]
[166]
Akiyama, T.; Shimo, Y.; Yanai, H.; Qin, J.; Ohshima, D.; Maruyama, Y.; Asaumi, Y.; Kitazawa, J.; Takayanagi, H.; Penninger, J.M.; Matsumoto, M.; Nitta, T.; Takahama, Y.; Inoue, J. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity, 2008, 29(3), 423-437.
[http://dx.doi.org/10.1016/j.immuni.2008.06.015]
[167]
Gardner, J.M.; Metzger, T.C.; McMahon, E.J.; Au-Yeung, B.B.; Krawisz, A.K.; Lu, W.; Price, J.D.; Johannes, K.P.; Satpathy, A.T.; Murphy, K.M.; Tarbell, K.V.; Weiss, A.; Anderson, M.S. Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4+ T cells. Immunity, 2013, 39(3), 560-572.
[http://dx.doi.org/10.1016/j.immuni.2013.08.005]
[168]
Anderson, M.S.; Venanzi, E.S.; Klein, L.; Chen, Z.; Berzins, S.P.; Turley, S.J.; von Boehmer, H.; Bronson, R.; Dierich, A.; Benoist, C.; Mathis, D. Projection of an immunological self shadow within the thymus by the aire protein. Science, 2002, 298(5597), 1395-1401.
[http://dx.doi.org/10.1126/science.1075958]
[169]
Handel, A.E.; Shikama-Dorn, N.; Zhanybekova, S.; Maio, S.; Graedel, A.N.; Zuklys, S.; Ponting, C.P.; Holländer, G.A. Comprehensively profiling the chromatin architecture of tissue restricted antigen expression in thymic epithelial cells over development. Front. Immunol., 2018, 9, 2120.
[http://dx.doi.org/10.3389/fimmu.2018.02120]
[170]
Sansom, S.N.; Shikama-Dorn, N.; Zhanybekova, S.; Nusspaumer, G.; Macaulay, I.C.; Deadman, M.E.; Heger, A.; Ponting, C.P.; Holländer, G.A. Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia. Genome Res., 2014, 24(12), 1918-1931.
[http://dx.doi.org/10.1101/gr.171645.113]
[171]
Tomofuji, Y.; Takaba, H.; Suzuki, H.I.; Benlaribi, R.; Martinez, C.D.P.; Abe, Y.; Morishita, Y.; Okamura, T.; Taguchi, A.; Kodama, T.; Takayanagi, H. Chd4 choreographs self-antigen expression for central immune tolerance. Nat. Immunol., 2020, 21(8), 892-901.
[http://dx.doi.org/10.1038/s41590-020-0717-2]
[172]
Eckler, M.J.; Larkin, K.A.; McKenna, W.L.; Katzman, S.; Guo, C.; Roque, R.; Visel, A.; Rubenstein, J.L.L.; Chen, B. Multiple conserved regulatory domains promote Fezf2 expression in the developing cerebral cortex. Neural Dev., 2014, 9(1), 6.
[http://dx.doi.org/10.1186/1749-8104-9-6]
[173]
Baran-Gale, J.; Morgan, M.D.; Maio, S.; Dhalla, F.; Calvo-Asensio, I.; Deadman, M.E.; Handel, A.E.; Maynard, A.; Chen, S.; Green, F.; Sit, R.V.; Neff, N.F.; Darmanis, S.; Tan, W.; May, A.P.; Marioni, J.C.; Ponting, C.P.; Holländer, G.A. Ageing compromises mouse thymus function and remodels epithelial cell differentiation. eLife, 2020, 9, e56221.
[http://dx.doi.org/10.7554/eLife.56221]
[174]
Green, H.N.; Mellanby, E. Vitamin A as an anti-infective agent. BMJ, 1928, 2(3537), 691-696.
[http://dx.doi.org/10.1136/bmj.2.3537.691]
[175]
Semba, R.D. Vitamin A and immunity to viral, bacterial and protozoan infections. Proc. Nutr. Soc., 1999, 58(3), 719-727.
[http://dx.doi.org/10.1017/S0029665199000944]
[176]
Raverdeau, M.; Mills, K.H.G. Modulation of T cell and innate immune responses by retinoic Acid. J. Immunol., 2014, 192(7), 2953-2958.
[http://dx.doi.org/10.4049/jimmunol.1303245]
[177]
Bernard, A.; Boumsell, L.; Hill, C. Joint Report of the First International Workshop on Human Leucocyte Differentiation Antigens by the Investigators of the Participating Laboratories; Springer: Berlin, Heidelberg, 1984.
[178]
Spencer, S.P.; Wilhelm, C.; Yang, Q.; Hall, J.A.; Bouladoux, N.; Boyd, A.; Nutman, T.B.; Urban, J.F., Jr; Wang, J.; Ramalingam, T.R.; Bhandoola, A.; Wynn, T.A.; Belkaid, Y. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science, 2014, 343(6169), 432-437.
[http://dx.doi.org/10.1126/science.1247606]
[179]
Dong, P.; Tao, Y.; Yang, Y.; Wang, W. Expression of retinoic acid receptors in intestinal mucosa and the effect of vitamin A on mucosal immunity. Nutrition, 2010, 26(7-8), 740-745.
[http://dx.doi.org/10.1016/j.nut.2009.08.011]
[180]
Kramer, T.R. Relationship between vitamin a status and t-lymphocyte responsiveness. J. Nutr. Immunol., 1996, 4(1-2), 77-85.
[181]
Carazo, A.; Macáková, K.; Matoušová, K.; Krčmová, L.K.; Protti, M.; Mladěnka, P. Vitamin a update: Forms, sources, kinetics, detection, function, deficiency, therapeutic use and toxicity. Nutrients, 2021, 13(5), 1703.
[http://dx.doi.org/10.3390/nu13051703]
[182]
Lykkesfeldt, J.; Michels, A.J.; Frei, B.; Vitamin, C. Adv. Nutr., 2014, 5(1), 16-18.
[http://dx.doi.org/10.3945/an.113.005157]
[183]
Uchio, R.; Hirose, Y.; Murosaki, S.; Yamamoto, Y.; Ishigami, A. High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice. Br. J. Nutr., 2015, 113(4), 603-609.
[http://dx.doi.org/10.1017/S0007114514003857]
[184]
Huijskens, M.J.A.J.; Walczak, M.; Koller, N.; Briedé, J.J.; Senden-Gijsbers, B.L.M.G.; Schnijderberg, M.C.; Bos, G.M.J.; Germeraad, W.T.V. Technical advance: Ascorbic acid induces development of double-positive T cells from human hematopoietic stem cells in the absence of stromal cells. J. Leukoc. Biol., 2014, 96(6), 1165-1175.
[http://dx.doi.org/10.1189/jlb.1TA0214-121RR]
[185]
Schmitt, T.M.; Zúñiga-Pflücker, J.C. Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity, 2002, 17(6), 749-756.
[http://dx.doi.org/10.1016/S1074-7613(02)00474-0]
[186]
Huijskens, M.J.A.J.; Walczak, M.; Sarkar, S.; Atrafi, F.; Senden-Gijsbers, B.L.M.G.; Tilanus, M.G.J.; Bos, G.M.J.; Wieten, L.; Germeraad, W.T.V. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy, 2015, 17(5), 613-620.
[http://dx.doi.org/10.1016/j.jcyt.2015.01.004]
[187]
Chambial, S.; Dwivedi, S.; Shukla, K.K.; John, P.J.; Sharma, P. Vitamin C in disease prevention and cure: An overview. Indian J. Clin. Biochem., 2013, 28(4), 314-328.
[http://dx.doi.org/10.1007/s12291-013-0375-3]
[188]
Sibaii, H.M.R.; El-Zayat, S.R.; Abd El-Shaheed, A.; Mahfouz, N.N.; Sallam, S.F.; El Azma, M.H. The hidden function of vitamin D. Open Access Maced. J. Med. Sci., 2016, 4(4), 591-595.
[http://dx.doi.org/10.3889/oamjms.2016.134]
[189]
Aranow, C. Vitamin D and the immune system. J. Investig. Med., 2011, 59(6), 881-886.
[http://dx.doi.org/10.2310/JIM.0b013e31821b8755]
[190]
Konijeti, G.G.; Arora, P.; Boylan, M.R.; Song, Y.; Huang, S.; Harrell, F.; Newton-Cheh, C.; O’Neill, D.; Korzenik, J.; Wang, T.J.; Chan, A.T. Vitamin D supplementation modulates t cell–mediated immunity in humans: Results from a randomized control trial. J. Clin. Endocrinol. Metab., 2016, 101(2), 533-538.
[http://dx.doi.org/10.1210/jc.2015-3599]
[191]
Deluca, H.F.; Cantorna, M.T.; Vitamin, D. Its role and uses in immunology. FASEB J., 2001, 15(14), 2579-2585.
[http://dx.doi.org/10.1096/fj.01-0433rev]
[192]
Chen, W.; Wang, J.P.; Huang, Y.Q. Effects of dietary n-6:n-3 polyunsaturated fatty acid ratio on cardiac antioxidative status, T-cell and cytokine mRNA expression in the thymus, and blood T lymphocyte subsets of broilers. Livest. Sci., 2012, 150(1-3), 114-120.
[http://dx.doi.org/10.1016/j.livsci.2012.08.008]
[193]
Moriguchi, S.; Miwa, H.; Okamura, M.; Maekawa, K.; Kishino, Y.; Maeda, K. Vitamin E is an important factor in T cell differentiation in thymus of F344 rats. J. Nutr. Sci. Vitaminol., 1993, 39(5), 451-463.
[http://dx.doi.org/10.3177/jnsv.39.451]
[194]
Chen, T.; Yuan, S.; Wan, X.; Zhan, L.; Yu, X.; Zeng, J.; Li, H.; Zhang, W.; Hu, X.; Ye, Y.; Hu, W. Chinese herb cinobufagin-reduced cancer pain is associated with increased peripheral opioids by invaded CD3/4/8 lymphocytes. Oncotarget, 2017, 8(7), 11425-11441.
[http://dx.doi.org/10.18632/oncotarget.14005]
[195]
Chen, Z. Clinical observation of cinobufacini injection used to treat moderate and advanced primary liver cancer. J. Chin. Integr. Med., 2003, 1(3), 184-186.
[http://dx.doi.org/10.3736/jcim20030311]
[196]
He, Y.L. Effects of Lycium barbarum polysaccharide on tumor microenvironment T-lymphocyte subsets and dendritic cells in H22-bearing mice. J. Chin. Integr. Med., 2005, 3(5), 374-377.
[http://dx.doi.org/10.3736/jcim20050511]
[197]
Chen, J.R.; Li, E-Q.; Dai, C-Q.; Yu, B.; Wu, X-L.; Huang, C-R.; Chen, X-Y. The inducible effect of LBP on maturation of dendritic cells and the related immune signaling pathways in hepatocellular carcinoma (HCC). Curr. Drug Deliv., 2012, 9(4), 414-420.
[http://dx.doi.org/10.2174/156720112801323107]
[198]
Polyak, S.J.; Morishima, C.; Shuhart, M.C.; Wang, C.C.; Liu, Y.; Lee, D.Y-W. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-κB signaling, and HCV infection by standardized silymarin. Gastroenterology, 2007, 132(5), 1925-1936.
[http://dx.doi.org/10.1053/j.gastro.2007.02.038]
[199]
Wang, M.; Wang, H.; Tang, Y.; Kang, D.; Gao, Y.; Ke, M.; Dou, J.; Xi, T.; Zhou, C. Effective inhibition of a Strongylocentrotus nudus eggs polysaccharide against hepatocellular carcinoma is mediated via immunoregulation in vivo. Immunol. Lett., 2011, 141(1), 74-82.
[http://dx.doi.org/10.1016/j.imlet.2011.08.001]
[200]
Long, S. GuangZhi, Y.; BaoJie, G.; Wei, X.; YanYong, H.; YingLi, W.; Yang, Z.; LiHua, L. Shikonin derivatives protect immune organs from damage and promote immune responses in vivo in tumour‐bearing mice. Phytother. Res., 2012, 26(1), 26-33.
[http://dx.doi.org/10.1002/ptr.3503]
[201]
Shu, G.; Yang, T.; Wang, C.; Su, H.; Xiang, M. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4+ T cells. Toxicol. Appl. Pharmacol., 2013, 269(3), 270-279.
[http://dx.doi.org/10.1016/j.taap.2013.02.019]
[202]
Huang, Z.; Wang, Y.; Chen, J.; Wang, R.; Chen, Q. Effect of Xiaoaiping injection on advanced hepatocellular carcinoma in patients. J. Tradit. Chin. Med., 2013, 33(1), 34-38.
[http://dx.doi.org/10.1016/S0254-6272(13)60097-7]
[203]
Han, L.; Yao, S.; Cao, S.; Mo, G.; Li, J.; Cao, Y.; Huang, F. Triterpenoid saponins from anemone flaccida suppress tumor cell proliferation by regulating MAPK, PD1/PDL1, and STAT3 signaling pathways and altering cancer metabolism. OncoTargets Ther., 2019, 12, 10917-10930.
[http://dx.doi.org/10.2147/OTT.S212666]
[204]
Zhang, Q.B.; Meng, X-T.; Jia, Q-A.; Bu, Y.; Ren, Z-G.; Zhang, B-H.; Tang, Z-Y. Herbal compound songyou yin and moderate swimming suppress growth and metastasis of liver cancer by enhancing immune function. Integr. Cancer Ther., 2016, 15(3), 368-375.
[http://dx.doi.org/10.1177/1534735415622011]
[205]
Zhu, Y.C. Effects of Shiquanyuzhentang on immunologic function of H(22) tumor-bearing mouse. Zhongguo Ying Yong Sheng Li Xue Za Zhi, 2017, 33(1), 51-55.
[206]
Chen, X.; Cao, Z.; Zhang, Y.; Li, J.; Wang, S.; Du, J.; Liao, L. Fuzheng qingjie granules inhibit growth of hepatoma cells via inducing mitochondria-mediated apoptosis and enhancing immune function. Integr. Cancer Ther., 2017, 16(3), 329-338.
[http://dx.doi.org/10.1177/1534735416654761]
[207]
Fu, B.; Zhai, X.; Xi, S.; Yue, L.; Wang, Y.; Qiu, Y.; Gong, Y.; Xu, Y.; Qian, L.; Huang, J.; Lu, D.; Huang, S.; Wang, J.; Zhou, J.; Wu, D.; Wang, Y. Safety evaluation of a new traditional chinese medical formula, ciji-hua’ai-baosheng II formula, in adult rodent models. Evid. Based Complement. Alternat. Med., 2019, 2019, 1-21.
[http://dx.doi.org/10.1155/2019/3659890]
[208]
Xi, S.; Fu, B.; Loy, G.; Minuk, G.Y.; Peng, Y.; Qiu, Y.; Zhai, X.; Wang, Y.; Li, P.; Gong, Y.; Wang, J.; Huang, S.; Lu, D.; Wang, Y. The effects of Ciji-Hua’ai-Baosheng on immune function of mice with H22 hepatocellular carcinoma receiving chemotherapy. Biomed. Pharmacother., 2018, 101, 898-909.
[http://dx.doi.org/10.1016/j.biopha.2018.03.027]
[209]
Zhou, J.Y.; Chen, M.; Wu, C-E.; Zhuang, Y-W.; Chen, Y-G.; Liu, S-L. The modified Si-Jun-Zi Decoction attenuates colon cancer liver metastasis by increasing macrophage cells. BMC Complement. Altern. Med., 2019, 19(1), 86.
[http://dx.doi.org/10.1186/s12906-019-2498-4]
[210]
Xu, H.; Wenjie, W.; Mu, Y.; Chengwei, D. Efficacy and safety of Chinese patent medicine (Jinlong capsule) in the treatment of advanced hepatocellular carcinoma: A meta-analysis. Biosci Rep., 2020, 40(1), BSR20194019.
[211]
Zhang, H.J. Effects of Jinlong Capsule on expressions of interleukin-2 and soluble interleukin-2 receptor in patients with primary liver cancer after transarterial chemoembolization therapy. J. Chin. Integr. Med., 2008, 6(9), 907-910.
[http://dx.doi.org/10.3736/jcim20080906]
[212]
Rayman, M.P. Selenium and human health. Lancet, 2012, 379(9822), 1256-1268.
[http://dx.doi.org/10.1016/S0140-6736(11)61452-9]
[213]
Arthur, J.R.; McKenzie, R.C.; Beckett, G.J. Selenium in the immune system. J. Nutr., 2003, 133(5), 1457S-1459S.
[http://dx.doi.org/10.1093/jn/133.5.1457S]
[214]
Ferenčík, M.; Ebringer, L. Modulatory effects of selenium and zinc on the immune system. Folia Microbiol., 2003, 48(3), 417-426.
[http://dx.doi.org/10.1007/BF02931378]
[215]
Kieliszek, M. Selenium–fascinating microelement, properties and sources in food. Molecules, 2019, 24(7), 1298.
[http://dx.doi.org/10.3390/molecules24071298]
[216]
Roohani, N. Zinc and its importance for human health: An integrative review. J. Res. Med. Sci., 2013, 18(2), 144-157.
[217]
Mocchegiani, E.; Santarelli, L.; Costarelli, L.; Cipriano, C.; Muti, E.; Giacconi, R.; Malavolta, M. Plasticity of neuroendocrine–thymus interactions during ontogeny and ageing: Role of zinc and arginine. Ageing Res. Rev., 2006, 5(3), 281-309.
[http://dx.doi.org/10.1016/j.arr.2006.06.001]
[218]
Nie, J.; Zhao, C.; Deng, L.; Chen, J.; Yu, B.; Wu, X.; Pang, P.; Chen, X. Efficacy of traditional Chinese medicine in treating cancer. Biomed. Rep., 2016, 4(1), 3-14.
[http://dx.doi.org/10.3892/br.2015.537]
[219]
Hsiao, W.; Liu, L. The role of traditional Chinese herbal medicines in cancer therapy--from TCM theory to mechanistic insights. Planta Med., 2010, 76(11), 1118-1131.
[http://dx.doi.org/10.1055/s-0030-1250186]
[220]
Hu, Y.; Wang, S.; Wu, X.; Zhang, J.; Chen, R.; Chen, M.; Wang, Y. Chinese herbal medicine-derived compounds for cancer therapy: A focus on hepatocellular carcinoma. J. Ethnopharmacol., 2013, 149(3), 601-612.
[http://dx.doi.org/10.1016/j.jep.2013.07.030]
[221]
Yang, L.; Yongchao, G.; Jupeng, G.; Hui, W.; Mohamed, A.F.; Simal-Gandara, J.; Yonghua, Z.; Shaoping, N.; Jianbo, X. Myricetin ameliorated prediabetes via immunomodulation and gut microbiota interaction. 2022, 3(4), 749-772.
[http://dx.doi.org/10.1002/fft2.152]
[222]
Del Cornò, M.; Gessani, S.; Conti, L. Shaping the innate immune response by dietary glucans: Any role in the control of cancer? Cancers, 2020, 12(1), 155.
[http://dx.doi.org/10.3390/cancers12010155]
[223]
Cao, C. Effects of lycium barbarum polysaccharides on immunity and metabolic syndrome associated with the modulation of gut microbiota. Review, 2022, 11(20), 3177.
[224]
Chen, J. Anti-tumour effects of polysaccharides isolated from Artemisia annua L by inducing cell apoptosis and immunomodulatory anti-hepatoma effects of polysaccharides. Afr. J. Tradit. Complement. Altern. Med., 2014, 11(1), 15-22.
[225]
Li, Y.; Wang, X.; Ma, X.; Liu, C.; Wu, J.; Sun, C. Natural polysaccharides and their derivates: A promising natural adjuvant for tumor immunotherapy. Front. Pharmacol., 2021, 12, 621813.
[http://dx.doi.org/10.3389/fphar.2021.621813]
[226]
Wang, X.Y. Gastroprotective polysaccharide from natural sources: Review on structure, mechanism, and structure–activity relationship, 2022, 4(4), 560-591.
[http://dx.doi.org/10.1002/fft2.172]
[227]
Sohretoglu, D.; Huang, S. Ganoderma lucidum polysaccharides as an anti-cancer agent. Anticancer. Agents Med. Chem., 2018, 18(5), 667-674.
[http://dx.doi.org/10.2174/1871520617666171113121246]
[228]
Mirlekar, B. Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy. SAGE Open Med., 2022, 10.
[http://dx.doi.org/10.1177/20503121211069012]
[229]
Rezalotfi, A.; Ahmadian, E.; Aazami, H.; Solgi, G.; Ebrahimi, M. Gastric cancer stem cells effect on Th17/Treg Balance; A bench to beside perspective. Front. Oncol., 2019, 9, 226.
[http://dx.doi.org/10.3389/fonc.2019.00226]
[230]
Du, B. A narrative review on conformational structure characterization of natural polysaccharides. Food Front., 2022, 3(4), 631-640.
[http://dx.doi.org/10.1002/fft2.150]
[231]
Yuan, E. Effects of complex extracts of traditional Chinese herbs on gastric mucosal injury in rats and potential underlying mechanism. Food Front., 2021, 2(3), 305-315.
[http://dx.doi.org/10.1002/fft2.73]
[232]
Some Drugs and Herbal Products. In: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; International Agency for Research on Cancer: Lyon, FR, 2016.
[233]
Singh, N.; Bhalla, M.; De Jager, P.; Gilca, M. An overview on ashwagandha: A Rasayana (rejuvenator) of Ayurveda. Afr. J. Tradit. Complement. Altern. Med., 2011, 8(S5), 208-213.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.9]
[234]
Tharakan, A. Immunomodulatory effect of withania somnifera (ashwagandha) extract-a randomized, double-blind, placebo controlled trial with an open label extension on healthy participants. J. Clin. Med., 2021, 10(16), 3644.
[235]
Alzohairy, M.A. Therapeutics role of azadirachta indica (neem) and their active constituents in diseases prevention and treatment. Evid. Based Complement. Alternat. Med., 2016, 2016, 1-11.
[http://dx.doi.org/10.1155/2016/7382506]
[236]
Guha, I.; Bhuniya, A.; Nandi, P.; Dasgupta, S.; Sarkar, A.; Saha, A.; Das, J.; Ganguly, N.; Ghosh, S.; Ghosh, T.; Sarkar, M.; Ghosh, S.; Majumdar, S.; Baral, R.; Bose, A. Neem leaf glycoprotein reverses tumor-induced and age-associated thymic involution to maintain peripheral CD8 + T cell pool. Immunotherapy, 2020, 12(11), 799-818.
[http://dx.doi.org/10.2217/imt-2019-0168]
[237]
Surjushe, A.; Vasani, R.; Saple, D.G. Aloe vera: A short review. Indian J. Dermatol., 2008, 53(4), 163-166.
[http://dx.doi.org/10.4103/0019-5154.44785]
[238]
Akev, N.; Turkay, G.; Can, A.; Gurel, A.; Yildiz, F.; Yardibi, H.; Ekiz, E.E.; Uzun, H. Tumour preventive effect of Aloe vera leaf pulp lectin (Aloctin I) on Ehrlich ascites tumours in mice. Phytother. Res., 2007, 21(11), 1070-1075.
[http://dx.doi.org/10.1002/ptr.2215]
[239]
Sharma, P.; Dwivedee, B.P.; Bisht, D.; Dash, A.K.; Kumar, D. The chemical constituents and diverse pharmacological importance of Tinospora cordifolia. Heliyon, 2019, 5(9), e02437.
[http://dx.doi.org/10.1016/j.heliyon.2019.e02437]
[240]
Singh, N.; Mahendra Singh, S.; Prakash; Singh, G. Restoration of thymic homeostasis in a tumor-bearing host by in vivo administration of medicinal herb Tinospora cordifolia. Immunopharmacol. Immunotoxicol., 2005, 27(4), 585-599.
[http://dx.doi.org/10.1080/08923970500416764]
[241]
Butnariu, M.; Coradini, C.Z. Evaluation of biologically active compounds from calendula officinalis flowers using spectrophotometry. Chem. Cent. J., 2012, 6(1), 35.
[http://dx.doi.org/10.1186/1752-153X-6-35]
[242]
Compendium of botanicals reported to contain naturally occuring substances of possible concern for human health when used in food and food supplements. EFSA J., 2012, 10(5), 2663.
[243]
Berges, C.; Fuchs, D.; Opelz, G.; Daniel, V.; Naujokat, C. Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms. Mol. Immunol., 2009, 46(15), 2892-2901.
[http://dx.doi.org/10.1016/j.molimm.2009.07.004]
[244]
Yang, J.; Sun, H.; Ma, J.; Song, Y.; Liu, Y.; Wang, Q.; Ma, S.; Cheng, X.; Wei, F. New phenolic constituents obtained from Polygonum multiflorum. Chin. Herb. Med., 2020, 12(3), 342-346.
[http://dx.doi.org/10.1016/j.chmed.2020.02.001]
[245]
Hong, F.; Xiao, W.; Ragupathi, G.; Lau, C.; Leung, P.; Yeung, K.; George, C.; Cassileth, B.; Kennelly, E.; Livingston, P. The known immunologically active components of Astragalus account for only a small proportion of the immunological adjuvant activity when combined with conjugate vaccines. Planta Med., 2011, 77(8), 817-824.
[http://dx.doi.org/10.1055/s-0030-1250574]
[246]
Wei, X.; Zhang, J.; Li, J.; Chen, S. Astragalus mongholicus and Polygonum multiflorum’s protective function against cyclophosphamide inhibitory effect on thymus. Am. J. Chin. Med., 2004, 32(5), 669-680.
[http://dx.doi.org/10.1142/S0192415X04002338]
[247]
Chaudhry, M.S.; Velardi, E.; Dudakov, J.A.; van den Brink, M.R.M. Thymus: The next (re)generation. Immunol. Rev., 2016, 271(1), 56-71.
[http://dx.doi.org/10.1111/imr.12418]
[248]
Williams, D.J.E. A healthy thymus enhances immunity to beat infections, prevent cancer, and extend lifespan. 2020. Available from: https://drjewilliams.com/blog/rejuvenate-your-thymus-gland/
[249]
Marvel, N. Clinical study of the biologically active peptide bioregulator vladonix. 2018. Available from: https://naturesmarvels.com/2018/12/13/clinical-study-of-the-biologically-active-peptide-bioregulator-vladonix
[250]
Gombart, A.F.; Pierre, A.; Maggini, S. A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nutrients, 2020, 12(1), 236.
[http://dx.doi.org/10.3390/nu12010236]
[251]
Teitelbaum, J. The single best immune system supplement available. 2023. Available from: https://www.rejuvenation-science.com/thymic-protein-a#:~:text=Thymic%20Protein%20A%2C%20the%20active,of%20by%20the%20immune%20system
[252]
Nusser, A. Sagar; Swann, J.B.; Krauth, B.; Diekhoff, D.; Calderon, L.; Happe, C.; Grün, D.; Boehm, T. Developmental dynamics of two bipotent thymic epithelial progenitor types. Nature, 2022, 606(7912), 165-171.
[http://dx.doi.org/10.1038/s41586-022-04752-8]
[253]
Mohtashami, M.; Li, Y.R.; Lee, C.R.; Zúñiga-Pflücker, J.C. Thymus reconstitution in young and aged mice is facilitated by in vitro-generated progenitor T cells. Front. Immunol., 2022, 13, 926773.
[http://dx.doi.org/10.3389/fimmu.2022.926773]
[254]
Varghese, J.E. Therapeutic effects of vitamin D and cancer: An overview. Food Front., 2021, 2(4), 417-425.
[http://dx.doi.org/10.1002/fft2.97]
[255]
Sangeetha, V.J. Zinc nutrition and human health: Overview and implications. eFood, 2022, 3(5), e17.
[http://dx.doi.org/10.1002/efd2.17]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy