Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Hepatocytes induce Foxp3+ regulatory T cells by Notch signaling | |
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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