IgA+ plasma cells in murine intestinal lamina propria as a positive regulator of Treg differentiation

[摘要] Continuousexposuretocommensalbacteriagivesrisetoacomplexintestinalimmunesystemthatmaintainslocaltolerance,whichrequiresFoxp3‐expressingTreg.Recently,theregulationofTFHfunctionbyplasmacellshasbeenreported,buteffectsofintestinalLP‐PCs,oneoftherichestplasmacellsinthebody,onTcelldifferentiationhavenotbeenstudied.Here,weinvestigatedwhetherIgA+LP‐PCsfrommurinesmallintestineshadeffectsonTcelldifferentiation.Surprisingly,whenIgA+LP‐PCswerecoculturedwithCD4+Tcells,Foxp3expressionwasincreasedsignificantlyinCD4+CD25−Tcells.ResultsusingtheTranswellcoculturesystemrevealedthatsolublefactorsfromLP‐PCs,TGF‐β,andRAwereinvolvedintheinductionofFoxp3expression.Furthermore,Foxp3+CD25−TcellsweredecreasedinPPafterintestinaldepletionofplasmacells.Inaddition,intestinalcolonytransferfromSPFtogerm‐freemicewasdemonstratedtogenerateIgA+LP‐PCsandFoxp3+TcellswithmeaningfulcorrelationinLP.WereportforthefirsttimethatIgA+LP‐PCsinduceFoxp3expressioninTcellsthroughTGF‐βandRA.LP‐PCsgeneratedbycommensalbacteriamayplayacrucialroleinintestinalimmunitythroughtheinductionofTreg,aswellasIgAproduction...

[学科分类] 生理学

[关键词] Foxp3;regulatory T cell;TGF‐βretinoic acid