RLR‐mediated production of interferon‐β by a human dendritic cell subset and its role in virus‐specific immunity

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

关键词: innate immunity;    RIG‐;    I‐;    like receptor;    inflammatory cytokine;    influenza;   

DOI  :  10.1189/jlb.0711360

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CytosolicRIG‐I‐likehelicases(RLR)arePRRsinvolvedintypeIIFNproductionandantiviralimmunity.Thisstudyfocusestothecomparisonoftheexpression,function,andsignalingcascadesassociatedtoRLRinthepreviouslyidentifiedCD14−DC‐SIGN+PPARγlowCD1a+andCD14lowDC‐SIGN+PPARγhighCD1a−humanmoDCsubsets.OurresultsrevealedthattheexpressionofRLRgenesandproteinsaswellastheactivityofthecoupledsignalingpathwaysaresignificantlyhigherintheCD1a+subsetthaninitsphenotypicallyandfunctionallydistinctcounterpart.SpecificactivationofRLRinmoDCsbypoly(I:C)orinfluenzaviruswasshowntoinducethesecretionofIFN‐βviaIRF3,whereasinductionofproinflammatorycytokineresponseswerepredominantlycontrolledbyTLR3.TherequirementofRLR‐mediatedsignalinginCD1a+moDCsforprimingnaïveCD8+Tlymphocytesandinducinginfluenzavirus‐specificcellularimmuneresponseswasconfirmedbyRIG‐I/MDA5silencing,whichabrogatedthesefunctions.Ourresultsdemonstratethesubset‐specificactivationofRLRandtheunderlyingmechanismsbehinditscytokinesecretionprofileandidentifyCD1a+moDCsasaninflammatorysubsetwithspecializedfunctionalactivities.WealsoprovideevidencethatthismigratoryDCsubsetcanbedetectedinhumantonsilandreactiveLNs...

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