Abstract
MDSCs play an important role in the induction of immune tolerance. Cytokines and chemokines (GM-CSF, IL-6) contributed to the expansion, accumulation of MDSCs, and MDSCs function through iNOS, arginase and PD-L1. MDSCs are recruited and regulated through JAK/STAT, mTOR and Raf/MEK/ERK signaling pathways. MDSCs’ immunosuppressive functions were realized through Tregs-mediated pathways and their direct suppression of immune cells. All of the above contribute to the MDSC-related immune tolerance in transplantation. MDSCs have huge potential in prolonging graft survival and reducing rejection through different ways and many other factors worthy to be further investigated are also introduced.
Keywords: Myeloid-derived suppressor cells, immune tolerance, transplantation, GM-CSF, CXCR2, JAK/STAT.
Graphical Abstract
[http://dx.doi.org/10.1038/bmt.2015.102] [PMID: 26039215]
[http://dx.doi.org/10.1126/science.1079490] [PMID: 12522256]
[http://dx.doi.org/10.1038/ni833] [PMID: 12244307]
[http://dx.doi.org/10.1038/nri3175] [PMID: 22437938]
[http://dx.doi.org/10.1038/nri2506] [PMID: 19197294]
[http://dx.doi.org/10.1038/nm1609] [PMID: 17603493]
[http://dx.doi.org/10.1111/j.1600-6143.2009.02757.x] [PMID: 19681826]
[http://dx.doi.org/10.4049/jimmunol.180.12.7898]
[http://dx.doi.org/10.3727/096368910X540621] [PMID: 21054938]
[http://dx.doi.org/10.1097/01.TP.0000442504.23885.f7] [PMID: 24642686]
[http://dx.doi.org/10.1038/nrrheum.2009.178] [PMID: 19798030]
[http://dx.doi.org/10.1189/jlb.3RU0316-144R] [PMID: 27354413]
[http://dx.doi.org/10.1084/jem.20151975] [PMID: 27811055]
[http://dx.doi.org/10.1200/JCO.2014.60.5121] [PMID: 26392095]
[http://dx.doi.org/10.1007/s00109-016-1398-z] [PMID: 26936474]
[http://dx.doi.org/10.3389/fimmu.2018.00282] [PMID: 29497426]
[http://dx.doi.org/10.1136/gutjnl-2017-313738] [PMID: 29196437]
[http://dx.doi.org/10.1189/jlb.2HI1113-611RR] [PMID: 24948701]
[http://dx.doi.org/10.1189/jlb.3CE0514-272R] [PMID: 25360039]
[http://dx.doi.org/10.1016/j.transproceed.2017.11.014] [PMID: 29407325]
[http://dx.doi.org/10.1101/cshperspect.a016295] [PMID: 25190079]
[http://dx.doi.org/10.1007/s00109-012-0916-x] [PMID: 22660275]
[http://dx.doi.org/10.1016/j.trim.2015.05.001] [PMID: 25968653]
[http://dx.doi.org/10.1016/j.trim.2015.02.001] [PMID: 25680847]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0045] [PMID: 16357187]
[http://dx.doi.org/10.1016/j.trim.2006.09.035] [PMID: 17331844]
[http://dx.doi.org/10.1007/s00262-011-1028-0] [PMID: 21644036]
[http://dx.doi.org/10.1182/blood-2010-06-287839] [PMID: 20807889]
[http://dx.doi.org/10.1172/JCI41628] [PMID: 20551515]
[http://dx.doi.org/10.1097/01.tp.0000185198.07663.ba] [PMID: 16340794]
[http://dx.doi.org/10.1002/eji.200838411] [PMID: 18792404]
[http://dx.doi.org/10.1097/TP.0b013e3181806a60] [PMID: 18724229]
[http://dx.doi.org/10.1084/jem.20050419] [PMID: 15967822]
[http://dx.doi.org/10.1038/ncomms1677] [PMID: 22334081]
[http://dx.doi.org/10.1016/j.coi.2014.09.004] [PMID: 25278425]
[http://dx.doi.org/10.1111/imr.12619] [PMID: 29247993]
[http://dx.doi.org/10.1002/eji.200939472] [PMID: 19750479]
[http://dx.doi.org/10.1016/j.it.2017.01.006] [PMID: 28254169]
[http://dx.doi.org/10.1111/imm.12483] [PMID: 25988395]
[http://dx.doi.org/10.1182/blood-2001-12-0303] [PMID: 12130517]
[http://dx.doi.org/10.1073/pnas.1431057100] [PMID: 12853576]
[http://dx.doi.org/10.1002/eji.200636031] [PMID: 16897816]
[http://dx.doi.org/10.1097/TP.0b013e318186fccd] [PMID: 18946352]
[http://dx.doi.org/10.1016/j.bbrc.2004.09.097] [PMID: 15474475]
[http://dx.doi.org/10.1016/S1471-4906(03)00132-7] [PMID: 12810105]
[http://dx.doi.org/10.1080/02841860410029708] [PMID: 15244248]
[http://dx.doi.org/10.4049/jimmunol.0900092]
[http://dx.doi.org/10.1084/jem.188.9.1603] [PMID: 9802972]
[http://dx.doi.org/10.1074/jbc.M110675200] [PMID: 11950832]
[http://dx.doi.org/10.2174/1381612043452893] [PMID: 15032692]
[http://dx.doi.org/10.1034/j.1600-065X.2002.18809.x] [PMID: 12445284]
[http://dx.doi.org/10.1111/ajt.13276] [PMID: 25943210]
[http://dx.doi.org/10.1371/journal.pone.0054824] [PMID: 23359812]
[http://dx.doi.org/10.1111/j.1600-065X.2008.00608.x] [PMID: 18364002]
[http://dx.doi.org/10.1038/15260] [PMID: 10545998]
[http://dx.doi.org/10.1073/pnas.1612920114] [PMID: 28096371]
[http://dx.doi.org/10.1146/annurev.immunol.26.021607.090331] [PMID: 18173375]
[http://dx.doi.org/10.1084/jem.20051776] [PMID: 16606670]
[http://dx.doi.org/10.1002/eji.200737583] [PMID: 17899549]
[http://dx.doi.org/10.4049/jimmunol.174.6.3408]
[http://dx.doi.org/10.1016/j.transproceed.2015.10.060] [PMID: 27320602]
[http://dx.doi.org/10.1097/01.TP.0000085010.39567.FB] [PMID: 14508368]
[http://dx.doi.org/10.1073/pnas.1719190115] [PMID: 29531094]
[http://dx.doi.org/10.1038/leu.2012.215] [PMID: 22828446]
[http://dx.doi.org/10.1016/j.celrep.2015.08.077] [PMID: 26411680]
[http://dx.doi.org/10.1128/MCB.01251-14] [PMID: 25452304]
[http://dx.doi.org/10.4049/jimmunol.182.3.1746]
[http://dx.doi.org/10.1016/j.imlet.2003.09.013] [PMID: 14687724]
[http://dx.doi.org/10.4049/jimmunol.1101512]
[http://dx.doi.org/10.1007/s10753-014-9910-5] [PMID: 24788988]
[http://dx.doi.org/10.4049/jimmunol.176.1.284]
[http://dx.doi.org/10.1172/JCI28828] [PMID: 17016559]
[http://dx.doi.org/10.1016/j.semcancer.2005.07.005] [PMID: 16168663]
[http://dx.doi.org/10.1038/nm1325] [PMID: 16288283]
[http://dx.doi.org/10.1016/S0165-5728(97)00226-9] [PMID: 9610678]
[http://dx.doi.org/10.1002/eji.201040667] [PMID: 21110319]
[http://dx.doi.org/10.1189/jlb.3A0115-030RR] [PMID: 26034207]
[http://dx.doi.org/10.1189/jlb.0613350] [PMID: 24319288]
[http://dx.doi.org/10.1189/jlb.1A1014-479R] [PMID: 25713087]
[http://dx.doi.org/10.4049/jimmunol.181.7.4666]
[http://dx.doi.org/10.1189/jlb.0913473] [PMID: 24569105]
[http://dx.doi.org/10.1172/JCI34739] [PMID: 18725988]
[http://dx.doi.org/10.1073/pnas.0905056106] [PMID: 19850869]
[http://dx.doi.org/10.4161/cbt.7.12.6944] [PMID: 18981735]
[http://dx.doi.org/10.1038/srep20250] [PMID: 26833095]
[http://dx.doi.org/10.1016/j.trim.2007.10.007] [PMID: 18158116]
[http://dx.doi.org/10.1046/j.1600-6143.2004.00673.x] [PMID: 15643982]
[http://dx.doi.org/10.1038/cmi.2017.5] [PMID: 28287112]
[http://dx.doi.org/10.1038/nri1027] [PMID: 12658268]
[http://dx.doi.org/10.1111/tri.12909] [PMID: 28012226]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1299] [PMID: 16424049]
[http://dx.doi.org/10.1111/ajt.12461] [PMID: 24103111]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3755] [PMID: 16818658]
[http://dx.doi.org/10.1111/ajt.14718] [PMID: 29509288]
[http://dx.doi.org/10.1111/j.1600-6143.2009.02847.x] [PMID: 19845585]
[http://dx.doi.org/10.4049/jimmunol.0902661]
[http://dx.doi.org/10.4049/jimmunol.179.2.977]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-0182]
[http://dx.doi.org/10.1016/j.coi.2010.01.021] [PMID: 20171075]
[http://dx.doi.org/10.1172/JCI89717] [PMID: 28650339]
[http://dx.doi.org/10.1016/j.imbio.2016.08.005] [PMID: 27523745]
[http://dx.doi.org/10.1097/CJI.0b013e31825be926]
[http://dx.doi.org/10.1111/ajt.12914] [PMID: 25311657]
[http://dx.doi.org/10.1016/j.coi.2008.02.003] [PMID: 18406591]
[http://dx.doi.org/10.2217/imt.11.37] [PMID: 21524168]
[http://dx.doi.org/10.1016/j.immuni.2007.08.014] [PMID: 17919943]
[http://dx.doi.org/10.1172/JCI81227] [PMID: 26389674]
[http://dx.doi.org/10.1016/j.it.2012.11.003] [PMID: 23228885]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0387]
[http://dx.doi.org/10.1016/j.celrep.2017.09.018] [PMID: 28978469]
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0927] [PMID: 25115301]
[http://dx.doi.org/10.1016/j.bbrc.2017.10.009] [PMID: 28986261]
[http://dx.doi.org/10.1016/j.bbmt.2017.08.017]
[PMID: 11406548]
[http://dx.doi.org/10.1007/s00109-003-0476-1] [PMID: 12928788]
[http://dx.doi.org/10.1016/j.trim.2017.02.004] [PMID: 28257995]
[http://dx.doi.org/10.1038/s41598-018-21856-2] [PMID: 29491381]
[http://dx.doi.org/10.3390/ijms19082357] [PMID: 30103447]
[http://dx.doi.org/10.1155/2016/4986797] [PMID: 27868073]
[http://dx.doi.org/10.4049/jimmunol.1303408]
[http://dx.doi.org/10.1016/j.semcancer.2012.01.011] [PMID: 22313874]
[http://dx.doi.org/10.1182/blood-2007-07-100404] [PMID: 17991807]
[http://dx.doi.org/10.1016/j.humimm.2015.10.015] [PMID: 26527508]