Hepatocytes induce Foxp3+ regulatory T cells by Notch signaling
[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...
[发布日期] [发布机构]
[效力级别] [学科分类] 生理学
[关键词] mouse;γ‐secretase;antigen‐presenting cells;conversion [时效性]
