Differential role of all‐trans retinoic acid in promoting the development of CD4+ and CD8+ regulatory T cells

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

关键词: TGF‐;    β;    all‐;    trans retinoic acid;    regulatory T cells;    Foxp3;    Autoimmunity;    GVHD;   

DOI  :  10.1189/jlb.0513297

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ItisknownthatATRApromotesthedevelopmentofTGF‐β‐inducedCD4+Foxp3+iTregs,whichplayavitalroleinthepreventionofautoimmunediseases;however,theroleofATRAinfacilitatingthedifferentiationandfunctionofCD8+Foxp3+iTregsremainselusive.Usingahead‐to‐headcomparison,wefoundthatATRApromotedexpressionofFoxp3anddevelopmentofCD4+iTregs,butitdidnotpromoteFoxp3expressiononCD8+cells.Usingastandardinvitroassay,wedemonstratedthatCD8+iTregsinducedbyTGF‐βandATRAwerenotsuperiortoCD8+iTregsinducedbyTGF‐βalone.IncGVHD,inatypicallupussyndromemodelwhereDBA2spleencellsweretransferredtoDBA2xC57BL/6F1mice,weobservedthatbothCD8+iTregsinducedbyTGF‐βandATRAandthoseinducedbyTGF‐βalonehadsimilartherapeuticeffects.ATRAdidnotboostbut,conversely,impairedthedifferentiationandfunctionofhumanCD8+iTregs.CD8+cellsexpressedtheATRAreceptorRARandrespondedtoATRA,similartoCD4+cells.WehaveidentifiedthedifferentialroleofATRAinpromotingFoxp3+TregsinCD4+andCD8+cellpopulations.TheseresultswillhelptodetermineaprotocolfordevelopingdifferentTregcellpopulationsandmayprovidenovelinsightsintoclinicalcelltherapyforpatientswithautoimmunediseasesandthoseneedingorgantransplantation...

【 授权许可】

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