Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness

[摘要] HumanbloodDCsencompasspDCsandtwosubsetsofmDCs:CD1c+mDCsandCD141+mDCs.TherareCD141+DCpopulationisthoughttobetheequivalentofmouseCD8α+cDCsthatplayasignificantroleinantigencross‐presentation.Here,weanalyzedbyQ‐PCRTLR1–10expressioninbloodDCsubsets.WhereasCD1c+DCsexpressallTLRexceptTLR9,CD141+DCspresentamorerestrictedpatternwithhighexpressionofTLR3and‐10,expressionofTLR1,‐2,‐6,and‐8,andlackofTLR4,‐5,‐7,and‐9.TheinvitroanalysisofisolatedmDCsubsetreponsivenesstoanextensivepanelofTLRligandsconfirmedtheseresults,withCD141+DCsrespondingonlytoTLR1/2,‐3,and‐7/8.Thecytokine/chemokineproductionprofileofisolatedCD141+DCswasalsomorerestricted,astheyproducedmainlyproinflammatorycytokinesbutnoIL‐12andtoalowerlevel,incomparisonwithCD1c+DCs,exceptforCXCL10,CCL5,andIFN‐β.Incontrast,withtheuseofawholebloodassay,wefoundthatCD141+DCsproduceIL‐12inresponsetoTLR1/2,‐3,andmoresurprisingly,‐9.Finally,bothmDCsubsetsarepotentinducersofTh1response,particularlyafterTLR3triggering.Takentogether,thesedataconfirmedfunctionaldifferencesbetweenbloodmDCsubsets.ThemajorresponseofCD141+mDCstoTLR3ligandandtheircytokineproductionpatternsuggestaroleforthesecellsinantiviralimmunity...

[学科分类] 生理学

[关键词] dendritic cells;CD141;Toll‐like receptors;cytokines