Review Article

Exosomes in Inflammatory Bowel Disease: What Have We Learned So Far?

Author(s): Haichao Wang, Chen Ye, Yaling Wu, Pengyu Yang, Chunqiu Chen, Zhanju Liu and Xiaolei Wang*

Volume 21, Issue 14, 2020

Page: [1448 - 1455] Pages: 8

DOI: 10.2174/1389450121666200428102330

Price: $65

Abstract

Inflammatory bowel disease (IBD) is an immune-mediated chronic inflammatory disease. Although the etiology is uncertain, there is marked disbalance of mucosal immune responses in part shaped by genetic susceptibility and intestinal microbial dysbiosis. Suppressing inflammatory activity adequately and maintaining this suppression are the main goals of current therapies. However, corticosteroids are only suitable for therapy of active disease, and the effects of immunosuppressive agents are mainly limited to maintenance of remission. Biologics have become widely available and provide therapeutic benefits to IBD patients. However, only a part of patients benefits from them. Thus, there is an urgent need for the development of new substances in the therapy of IBD. Exosomes are nanosized lipid vesicles identified recently. They are secreted from all living cells and then distributed in various human body fluids. The components, such as microRNAs and functional proteins, secreted by exosomes in different cells have been reported to be involved in the pathogenesis of IBD. Therefore, exosomes have the potential to become appealing particles in treating IBD as a cell-free therapeutic approach as well as biomarkers for diagnosis and monitoring disease status. Further studies are needed to investigate the practicality, safety and desirable effects of exosomes in clinical applications in IBD.

Keywords: Exosomes, inflammatory bowel disease, pathogenesis, cell-free therapy, clinical application, microRNAs.

Graphical Abstract

[1]
Coskun M, Vermeire S, Nielsen OH. Novel targeted therapies for inflammatory bowel disease. Trends Pharmacol Sci 2017; 38(2): 127-42. [http://dx.doi.org/10.1016/j.tips.2016.10.014 ]. [PMID: 27916280].
[2]
Zhou Y, Xu ZZ, He Y, et al. Gut microbiota offers universal biomarkers across ethnicity in inflammatory bowel disease diagnosis and infliximab response prediction. mSystems 2018; 3(1): e00188-17.
[http://dx.doi.org/10.1128/mSystems.00188-17 ] [PMID: 29404425]
[3]
Uranga JA, López-Miranda V, Lombó F, Abalo R. Food, nutrients and nutraceuticals affecting the course of inflammatory bowel disease. Pharmacol Rep 2016; 68(4): 816-26.
[http://dx.doi.org/10.1016/j.pharep.2016.05.002 ] [PMID: 27267792]
[4]
Gisbert JP, Marín AC, McNicholl AG, Chaparro M. Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed. Aliment Pharmacol Ther 2015; 41(7): 613-23.
[http://dx.doi.org/10.1111/apt.13083 ] [PMID: 25652884]
[5]
Tsuchiya A, Kojima Y, Ikarashi S, et al. Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases. Inflamm Regen 2017; 37: 16.
[http://dx.doi.org/10.1186/s41232-017-0045-6 ] [PMID: 29259715]
[6]
Okamoto R, Watanabe M. Investigating cell therapy for inflammatory bowel disease. Expert Opin Biol Ther 2016; 16(8): 1015-23.
[http://dx.doi.org/10.1080/14712598.2016.1177019 ] [PMID: 27113391]
[7]
Gross JC, Chaudhary V, Bartscherer K, Boutros M. Active Wnt proteins are secreted on exosomes. Nat Cell Biol 2012; 14(10): 1036-45.
[http://dx.doi.org/10.1038/ncb2574 ] [PMID: 22983114]
[8]
Carrière J, Bretin A, Darfeuille-Michaud A, Barnich N, Nguyen HT. Exosomes released from cells infected with crohn’s disease-associated adherent-invasive escherichia coli activate host innate immune responses and enhance bacterial intracellular replication. Inflamm Bowel Dis 2016; 22(3): 516-28.
[http://dx.doi.org/10.1097/MIB.0000000000000635 ] [PMID: 26595556]
[9]
Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W. Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 2015; 40: 72-81.
[http://dx.doi.org/10.1016/j.semcdb.2015.02.009 ] [PMID: 25724562]
[10]
Tran TH, Mattheolabakis G, Aldawsari H, Amiji M. Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases. Clin Immunol 2015; 160(1): 46-58.
[http://dx.doi.org/10.1016/j.clim.2015.03.021 ] [PMID: 25842185]
[11]
Mitsuhashi S, Feldbrügge L, Csizmadia E, Mitsuhashi M, Robson SC, Moss AC. Luminal extracellular vesicles (evs) in inflammatory bowel disease (ibd) exhibit proinflammatory effects on epithelial cells and macrophages. Inflamm Bowel Dis 2016; 22(7): 1587-95.
[http://dx.doi.org/10.1097/MIB.0000000000000840 ] [PMID: 27271497]
[12]
Zheng X, Chen F, Zhang Q, et al. Salivary exosomal PSMA7: a promising biomarker of inflammatory bowel disease. Protein Cell 2017; 8(9): 686-95.
[http://dx.doi.org/10.1007/s13238-017-0413-7 ] [PMID: 28523434]
[13]
Xu AT, Lu JT, Ran ZH, Zheng Q. Exosome in intestinal mucosal immunity. J Gastroenterol Hepatol 2016; 31(10): 1694-9.
[http://dx.doi.org/10.1111/jgh.13413 ] [PMID: 27061439]
[14]
Leoni G, Neumann PA, Kamaly N, et al. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest 2015; 125(3): 1215-27.
[http://dx.doi.org/10.1172/JCI76693 ] [PMID: 25664854]
[15]
Wu Y, Qiu W, Xu X, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease in mice through ubiquitination. Am J Transl Res 2018; 10(7): 2026-36.
[PMID: 30093940]
[16]
Mao F, Wu Y, Tang X, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve inflammatory bowel disease in mice. BioMed Res Int 2017.; 20175356760
[http://dx.doi.org/10.1155/2017/5356760 ] [PMID: 28589143]
[17]
Yu Q, Zhang S, Chao K, et al. E3 Ubiquitin ligase RNF183 Is a Novel Regulator in Inflammatory Bowel Disease. J Crohn’s Colitis 2016; 10(6): 713-25.
[http://dx.doi.org/10.1093/ecco-jcc/jjw023 ] [PMID: 26818663]
[18]
Song JY, Kang HJ, Hong JS, et al. Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by re-polarizing intestinal macrophages. Sci Rep 2017; 7(1): 9412.
[http://dx.doi.org/10.1038/s41598-017-09827-5 ] [PMID: 28842625]
[19]
Baghaei K, Tokhanbigli S, Asadzadeh H, Nmaki S, Reza Zali M, Hashemi SM. Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases. J Cell Physiol 2019; 234(7): 9910-26.
[http://dx.doi.org/10.1002/jcp.27934 ] [PMID: 30536895]
[20]
Natasha G, Gundogan B, Tan A, et al. Exosomes as immunotheranostic nanoparticles. Clin Ther 2014; 36(6): 820-9.
[http://dx.doi.org/10.1016/j.clinthera.2014.04.019 ] [PMID: 24863261]
[21]
Ostrowski M, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 2010; 12(1): 19-30. sup pp 1-13.
[http://dx.doi.org/10.1038/ncb2000]
[22]
Yu S, Cao H, Shen B, Feng J. Tumor-derived exosomes in cancer progression and treatment failure. Oncotarget 2015; 6(35): 37151-68.
[http://dx.doi.org/10.18632/oncotarget.6022 ] [PMID: 26452221]
[23]
Beninson LA, Fleshner M. Exosomes: an emerging factor in stress-induced immunomodulation. Semin Immunol 2014; 26(5): 394-401.
[http://dx.doi.org/10.1016/j.smim.2013.12.001 ] [PMID: 24405946]
[24]
Taverna S, Pucci M, Alessandro R. Extracellular vesicles: small bricks for tissue repair/regeneration. Ann Transl Med 2017; 5(4): 83.
[http://dx.doi.org/10.21037/atm.2017.01.53 ] [PMID: 28275628]
[25]
Sato-Kuwabara Y, Melo SA, Soares FA, Calin GA. The fusion of two worlds: non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications. (Review) Int J Oncol 2015; 46(1): 17-27.
[http://dx.doi.org/10.3892/ijo.2014.2712 ] [PMID: 25338714]
[26]
Westhoff D, Witlox J, van Aalst C, et al. Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study. BBA Clin 2015; 4: 115-22.
[http://dx.doi.org/10.1016/j.bbacli.2015.10.002 ] [PMID: 26675981]
[27]
Wang X, Wang H, Cao J, Ye C. Exosomes from adipose-derived stem cells promotes vegf-c-dependent lymphangiogenesis by regulating mirna-132/tgf-β pathway. Cell Physiol Biochem 2018; 49(1): 160-71.
[http://dx.doi.org/10.1159/000492851 ] [PMID: 30134228]
[28]
Lippai D, Bala S, Catalano D, Kodys K, Szabo G. Micro-RNA-155 deficiency prevents alcohol-induced serum endotoxin increase and small bowel inflammation in mice. Alcohol Clin Exp Res 2014; 38(8): 2217-24.
[http://dx.doi.org/10.1111/acer.12483 ] [PMID: 25156614]
[29]
Alexander M, Hu R, Runtsch MC, et al. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun 2015; 6: 7321.
[http://dx.doi.org/10.1038/ncomms8321 ] [PMID: 26084661]
[30]
McDonald MK, Tian Y, Qureshi RA, et al. Functional significance of macrophage-derived exosomes in inflammation and pain. Pain 2014; 155(8): 1527-39.
[http://dx.doi.org/10.1016/j.pain.2014.04.029 ] [PMID: 24792623]
[31]
Tian T, Zhou Y, Feng X, et al. MicroRNA-16 is putatively involved in the NF-κB pathway regulation in ulcerative colitis through adenosine A2a receptor (A2aAR) mRNA targeting. Sci Rep 2016; 6: 30824.
[http://dx.doi.org/10.1038/srep30824 ] [PMID: 27476546]
[32]
Chen L, Yang W, Guo Y, et al. Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis. PLoS One 2017; 12(9); e0185406
[http://dx.doi.org/10.1371/journal.pone.0185406 ] [PMID: 28945793]
[33]
Lucafò M, Di Silvestre A, Romano M, et al. Role of the long non-coding rna growth arrest-specific 5 in glucocorticoid response in children with inflammatory bowel disease. Basic Clin Pharmacol Toxicol 2018; 122(1): 87-93.
[http://dx.doi.org/10.1111/bcpt.12851 ] [PMID: 28722800]
[34]
Bakirtzi K, Man Law IK, Fang K, Iliopoulos D, Pothoulakis C. MiR-21 in Substance P-induced exosomes promotes cell proliferation and migration in human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 2019; 317(6): G802-10.
[http://dx.doi.org/10.1152/ajpgi.00043.2019 ] [PMID: 31545921]
[35]
Okoye IS, Coomes SM, Pelly VS, et al. Microrna-containing t-regulatory-cell-derived exosomes suppress pathogenic T Helper 1 Cells. Immunity 2014; 41(3): 503.
[http://dx.doi.org/10.1016/j.immuni.2014.08.008 ] [PMID: 28903020]
[36]
Wong WY, Lee MM, Chan BD, et al. Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages. Proteomics 2016; 16(7): 1131-45.
[http://dx.doi.org/10.1002/pmic.201500174 ] [PMID: 26806198]
[37]
Lai Y, Xue J, Liu CW, et al. Serum metabolomics identifies altered bioenergetics, signaling cascades in parallel with exposome markers in crohn’s disease. Molecules 2019; 24(3); E449
[http://dx.doi.org/10.3390/molecules24030449 ] [PMID: 30691236]
[38]
Van Niel G, Mallegol J, Bevilacqua C, et al. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut 2003; 52(12): 1690-7.
[http://dx.doi.org/10.1136/gut.52.12.1690 ] [PMID: 14633944]
[39]
Nata T, Fujiya M, Ueno N, et al. MicroRNA-146b improves intestinal injury in mouse colitis by activating nuclear factor-κB and improving epithelial barrier function. J Gene Med 2013; 15(6-7): 249-60.
[http://dx.doi.org/10.1002/jgm.2717 ] [PMID: 23813877]
[40]
Zheng B, Yin WN, Suzuki T, et al. Exosome-Mediated miR-155 Transfer from Smooth Muscle Cells to Endothelial Cells Induces Endothelial Injury and Promotes Atherosclerosis. Mol Ther 2017; 25(6): 1279-94.
[http://dx.doi.org/10.1016/j.ymthe.2017.03.031 ] [PMID: 28408180]
[41]
Das I, Png CW, Oancea I, et al. Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins. J Exp Med 2013; 210(6): 1201-16.
[http://dx.doi.org/10.1084/jem.20121268 ] [PMID: 23650437]
[42]
Petit CS, et al. Requirement of cellular prion protein for intestinal barrier function and mislocalization in patients with inflammatory bowel disease. Gastroenterology 2012; 143(1): 122-132 e15.
[http://dx.doi.org/10.1053/j.gastro.2012.03.029]
[43]
Skotland T, Sandvig K, Llorente A. Lipids in exosomes: Current knowledge and the way forward. Prog Lipid Res 2017; 66: 30-41.
[http://dx.doi.org/10.1016/j.plipres.2017.03.001 ] [PMID: 28342835]
[44]
Eom T, Kim YS, Choi CH, Sadowsky MJ, Unno T. Current understanding of microbiota- and dietary-therapies for treating inflammatory bowel disease. J Microbiol 2018; 56(3): 189-98.
[http://dx.doi.org/10.1007/s12275-018-8049-8 ] [PMID: 29492876]
[45]
Asea A, Rehli M, Kabingu E, et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 2002; 277(17): 15028-34.
[http://dx.doi.org/10.1074/jbc.M200497200 ] [PMID: 11836257]
[46]
Samborski P, Grzymisławski M. The role of hsp70 heat shock proteins in the pathogenesis and treatment of inflammatory bowel diseases. Adv Clin Exp Med 2015; 24(3): 525-30.
[http://dx.doi.org/10.17219/acem/44144 ] [PMID: 26467144]
[47]
Lai RC, Yeo RW, Tan KH, Lim SK. Exosomes for drug delivery - a novel application for the mesenchymal stem cell. Biotechnol Adv 2013; 31(5): 543-51.
[http://dx.doi.org/10.1016/j.biotechadv.2012.08.008 ] [PMID: 22959595]
[48]
Burke M, Choksawangkarn W, Edwards N, Ostrand-Rosenberg S, Fenselau C. Exosomes from myeloid-derived suppressor cells carry biologically active proteins. J Proteome Res 2014; 13(2): 836-43.
[http://dx.doi.org/10.1021/pr400879c ] [PMID: 24295599]
[49]
Liang X, Zhang L, Wang S, Han Q, Zhao RC. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J Cell Sci 2016; 129(11): 2182-9.
[http://dx.doi.org/10.1242/jcs.170373 ] [PMID: 27252357]
[50]
Korolkova OY, Myers JN, Pellom ST, Wang L, M’Koma AE. Characterization of serum cytokine profile in predominantly colonic inflammatory bowel disease to delineate ulcerative and crohn’s colitides. Clin Med Insights Gastroenterol 2015; 8: 29-44.
[http://dx.doi.org/10.4137/CGast.S20612 ] [PMID: 26078592]
[51]
Cai Z, Zhang W, Yang F, et al. Immunosuppressive exosomes from TGF-β1 gene-modified dendritic cells attenuate Th17-mediated inflammatory autoimmune disease by inducing regulatory T cells. Cell Res 2012; 22(3): 607-10.
[http://dx.doi.org/10.1038/cr.2011.196 ] [PMID: 22157651]
[52]
Yang X, Meng S, Jiang H, Chen T, Wu W. Exosomes derived from interleukin-10-treated dendritic cells can inhibit trinitrobenzene sulfonic acid-induced rat colitis. Scand J Gastroenterol 2010; 45(10): 1168-77.
[http://dx.doi.org/10.3109/00365521.2010.490596 ] [PMID: 20469967]
[53]
Buck AH, Coakley G, Simbari F, et al. Erratum: Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat Commun 2015; 6: 8772.
[http://dx.doi.org/10.1038/ncomms9772 ] [PMID: 26490107]
[54]
Lee M, Jeong SY, Ha J, et al. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo. Biochem Biophys Res Commun 2014; 446(4): 983-9.
[http://dx.doi.org/10.1016/j.bbrc.2014.03.051 ] [PMID: 24657442]
[55]
Ma ZJ, Wang YH, Li ZG, et al. Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis. Int J Stem Cells 2019; 12(3): 440-8.
[http://dx.doi.org/10.15283/ijsc18139 ] [PMID: 31242720]
[56]
Wang Y, Tian J, Tang X, et al. Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice. Oncotarget 2016; 7(13): 15356-68.
[http://dx.doi.org/10.18632/oncotarget.7324 ] [PMID: 26885611]
[57]
Wang L, Yu Z, Wan S, et al. Exosomes derived from dendritic cells treated with schistosoma japonicum soluble egg antigen attenuate dss-induced colitis. Front Pharmacol 2017; 8: 651.
[http://dx.doi.org/10.3389/fphar.2017.00651 ] [PMID: 28959207]

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