Dendritic cells activated by double‐stranded RNA induce arthritis via autocrine type I IFN signaling. Issue 4 (4th December 2013)

• Record Type: Journal Article
• Authors: Narendra, Sudeep Chenna; Chalise, Jaya Prakash; Höök, Nina; Magnusson, Mattias
• Is Part Of: Journal of leukocyte biology. Volume 95:Issue 4(2014)
• Page Start: 661
• Page End: 666
• Publication Date: 2013-12-04
• Subjects: viral nucleic acids -- cytokines -- joint inflammation; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.0613320
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Type I IFN‐dependent and ‐independent pathways regulate arthritis activated by dsRNA‐stimulated DC. 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.