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

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

关键词: viral nucleic acids;    cytokines;    joint inflammation;   

DOI  :  10.1189/jlb.0613320

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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...

【 授权许可】

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