Recovery from experimental autoimmune uveitis promotes induction of antiuveitic inducible Tregs

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: neuroimmunomodulation;    melanocortins;    adenosine;    ocular immunobiology;    suppressor cells;   

DOI  :  10.1189/jlb.3A1014-466RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TherecoveryofEAU,amousemodelofendogenoushumanautoimmuneuveitis,ismarkedwiththeemergenceofautoantigen‐specificregulatoryimmunityinthespleenthatprotectsthemicefromrecurrenceofEAU.Thisregulatoryimmunityismediatedbyamelanocortin‐drivensuppressorAPCthatpresentsautoantigenandusesadenosinetoactivateanantigen‐specificCD4+TregsthroughtheA2Ar.Thesecellsarehighlyeffectiveinsuppressinguveitis,andtheyappeartobeinducibleTregs.Inthisstudy,wedeterminedwhethertheyareinducibleornaturalTregsandidentifiedthedependentmechanismforthefunctionofthesepost‐EAUTregs.Thepost‐EAUspleenCD25+CD4+TcellsweresortedforNRP‐1expressionandtransferredtorecipientmiceimmunizedforEAU.ThesortedNRP‐1−,butnottheNRP‐1+,TregssuppressedEAU.TheseNRP‐1−TregscoexpressPD‐1andPD‐L1.TreatmentofnaiveAPCswithα‐MSHpromotedaregulatoryAPCthatinducedCD25+CD4+TregsinaCD73‐dependentmanner.TheseTregswerePD‐L1+PD‐1+NRP‐1−FOXP3+HELIOS−andsuppressedEAUwhentransferredtorecipientmice.Incontrast,PD‐1−TcellsdidnotsuppressEAU,indicatingthatPD‐1isnecessaryforthesuppressiveactivityofiTregs.Moreover,theseTregsdidnotsuppresseffectorTcellswhenthePD/‐1/PD‐L1pathwaywasblocked.Theseresultsdemonstratethatpost‐EAUTregsareinducibleTregs,whichuseaPD‐1/PD‐L1mechanismtosuppressdisease...

【 授权许可】

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