Hepatocytes induce Foxp3+ regulatory T cells by Notch signaling

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

关键词: mouse;    γ;    ‐;    secretase;    antigen‐;    presenting cells;    conversion;   

DOI  :  10.1189/jlb.2AB0613-342RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theliverplaysapivotalroleinmaintainingimmunologicaltolerance,althoughtheexactmolecularmechanismisstilllargelyunknown.TheinductionofsystemictolerancebyliverresidentAPCshasbeenattributedtoperipheraldeletionandtotheinductionofTregs.HCs,theparenchymalcellsintheliver,couldfunctionasnonprofessionalAPCsandinteractandestablishcell–cellcontactwithTlymphocytes.WehypothesizedthatHCsfromhealthyorregeneratedliversmaycontributetoinductionoffunctionalTregs.Here,weshowthatmurineHCsinducedFoxp3+TregswithinCD4+Tcellsinvitro,whichincreasedinthepresenceofTGF‐β.Interestingly,afurtherFoxp3+TregexpansionwasobservedifHCswereisolatedfromregeneratedlivers.Additionally,theinductionofFoxp3+TregswasassociatedwiththeNotchsignalingpathway,astheabilityofHCstoenhanceFoxp3wasabolishedbyγ‐secretaseinhibition.Furthermore,HC‐iTregsshowedabilitytosuppresstheproliferativeresponseofCD4+Tcellstoanti‐CD3stimulationinvitro.Thus,HCsmayplayapivotalroleintheinductionoftoleranceviaNotch‐mediatedconversionofCD4+TcellsintoFoxp3+TregsuponTCRstimulation...

【 授权许可】

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