| First Author | Narendra SC | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 4 | Pages | 661-6 |
| PubMed ID | 24304616 | Mgi Jnum | J:211874 |
| Mgi Id | MGI:5576831 | Doi | 10.1189/jlb.0613320 |
| Citation | Narendra SC, et al. (2014) Dendritic cells activated by double-stranded RNA induce arthritis via autocrine type I IFN signaling. J Leukoc Biol 95(4):661-6 |
| abstractText | 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-alpha, 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. |
