| First Author | Schmitt H | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 8 | Pages | 1627-44 |
| PubMed ID | 27377589 | Mgi Jnum | J:236472 |
| Mgi Id | MGI:5806183 | Doi | 10.1084/jem.20160189 |
| Citation | Schmitt H, et al. (2016) Siglec-H protects from virus-triggered severe systemic autoimmunity. J Exp Med 213(8):1627-44 |
| abstractText | It is controversial whether virus infections can contribute to the development of autoimmune diseases. Type I interferons (IFNs) are critical antiviral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus. Type I IFN is mainly produced by plasmacytoid dendritic cells (pDCs). The secretion of type I IFN of pDCs is modulated by Siglec-H, a DAP12-associated receptor on pDCs. In this study, we show that Siglec-H-deficient pDCs produce more of the type I IFN, IFN-alpha, in vitro and that Siglec-H knockout (KO) mice produce more IFN-alpha after murine cytomegalovirus (mCMV) infection in vivo. This did not impact control of viral replication. Remarkably, several weeks after a single mCMV infection, Siglec-H KO mice developed a severe form of systemic lupus-like autoimmune disease with strong kidney nephritis. In contrast, uninfected aging Siglec-H KO mice developed a mild form of systemic autoimmunity. The induction of systemic autoimmune disease after virus infection in Siglec-H KO mice was accompanied by a type I IFN signature and fully dependent on type I IFN signaling. These results show that Siglec-H normally serves as a modulator of type I IFN responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. |
