Dendritic cells activated by double‐stranded RNA induce arthritis via autocrine type I IFN signaling

[摘要] ViraldsRNAcanbefoundatthesiteofinflammationinRApatients,andintra‐articularinjectionofdsRNAinducesarthritisbyactivatingtypeIIFNsignalinginmice.Further,DCs,amajorsourceofIFN‐α,canbefoundinthesynoviumofRApatients.WethereforedeterminedtheoccurrenceofDCsindsRNA‐inducedarthritisandtheirabilitytoinducearthritis.Here,weshow,byimmunohistochemistry,thatcellsexpressingthepan‐DCmarkerCD11candthepDCmarker120G8arepresentintheinflamedsynoviumindsRNA‐inducedarthritis.Flt3L‐generatedandsplenicDCspreactivatedwithdsRNAbeforeintra‐articularinjection,butnotmock‐stimulatedcells,clearlyinducedarthritis.InductionofarthritiswasdependentontypeIIFNsignalinginthedonorDCs,whereasIFNARexpressionintherecipientwasnotrequired.SortingoftheFlt3L‐DCpopulationintocDCs(CD11c+,PDCA‐1−)andpDCs(CD11c+,PDCA‐1+)revealedthatbothsubtypeswerearthritogenicandproducedtypeIIFNiftreatedwithdsRNA.Takentogether,theseresultsdemonstratethatviralnucleicacidscanelicitarthritisbyactivatingtypeIIFNsignalinginDCs.Oncetriggered,autocrinetypeIIFNsignalingindsRNA‐activatedDCsissufficienttopropagatearthritis...

[学科分类] 生理学

[关键词] viral nucleic acids;cytokines;joint inflammation