Schmitt H, Sell S, Koch J, Seefried M, Sonnewald S, Daniel C, Winkler T, Nitschke L (2016)
Publication Status: Published
Publication Type: Journal article
Publication year: 2016
Publisher: ROCKEFELLER UNIV PRESS
Book Volume: 213
Pages Range: 1627-1644
Journal Issue: 8
DOI: 10.1084/jem.20160189
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.
APA:
Schmitt, H., Sell, S., Koch, J., Seefried, M., Sonnewald, S., Daniel, C.,... Nitschke, L. (2016). Siglec-H protects from virus-triggered severe systemic autoimmunity. Journal of Experimental Medicine, 213(8), 1627-1644. https://doi.org/10.1084/jem.20160189
MLA:
Schmitt, Heike, et al. "Siglec-H protects from virus-triggered severe systemic autoimmunity." Journal of Experimental Medicine 213.8 (2016): 1627-1644.
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