title: Dendritic cells activated by double-stranded RNA induce arthritis via autocrine type I IFN signaling.
abstract: Viral dsRNA can be found at the site of inflammation in RA patients, and intra-articular injection of dsRNA induces arthritis by activating type I IFN signaling in mice. Further, DCs, a major source of IFN-α, can be found in the synovium of RA patients. We therefore determined the occurrence of DCs in dsRNA-induced arthritis and their ability to induce arthritis. Here, we show, by immunohistochemistry, that cells expressing the pan-DC marker CD11c and the pDC marker 120G8 are present in the inflamed synovium in dsRNA-induced arthritis. Flt3L-generated and splenic DCs preactivated with dsRNA before intra-articular injection, but not mock-stimulated cells, clearly induced arthritis. Induction of arthritis was dependent on type I IFN signaling in the donor DCs, whereas IFNAR expression in the recipient was not required. Sorting of the Flt3L-DC population into cDCs (CD11c(+), PDCA-1(-)) and pDCs (CD11c(+), PDCA-1(+)) revealed that both subtypes were arthritogenic and produced type I IFN if treated with dsRNA. Taken together, these results demonstrate that viral nucleic acids can elicit arthritis by activating type I IFN signaling in DCs. Once triggered, autocrine type I IFN signaling in dsRNA-activated DCs is sufficient to propagate arthritis.
authors.affiliation: 1.Dept. of Clinical & Experimental Medicine, Linköping University, 581 85-Linköping, Sweden. sudeep.chenna.narendra@liu.se.
authors.forename: Sudeep Chenna
authors.initials: SC
authors.lastname: Narendra
authors.forename: Jaya Prakash
authors.initials: JP
authors.lastname: Chalise
authors.forename: Nina
authors.initials: N
authors.lastname: Höök
authors.forename: Mattias
authors.initials: M
authors.lastname: Magnusson
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology* / Q000276:immunology; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007370:Interferon Type I / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D039521:CD11c Antigen; D007370:Interferon Type I; D008565:Membrane Proteins; D012330:RNA, Double-Stranded; C084881:flt3 ligand protein
keywords: cytokines; joint inflammation; viral nucleic acids