Siglec-H protects from virus-triggered severe systemic autoimmunity

Journal article


Publication Details

Author(s): Schmitt H, Sell S, Koch J, Seefried M, Sonnewald S, Daniel C, Winkler T, Nitschke L
Journal: Journal of Experimental Medicine
Publisher: ROCKEFELLER UNIV PRESS
Publication year: 2016
Volume: 213
Journal issue: 8
Pages range: 1627-1644
ISSN: 0022-1007


Abstract

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.


FAU Authors / FAU Editors

Daniel, Christoph Prof. Dr.
Nephropathologische Abteilung im Pathologischen Institut
Koch, Julia
Lehrstuhl für Genetik
Nitschke, Lars Prof. Dr.
Professur für Genetik
Schmitt, Heike Dr. rer. nat.
Professur für Genetik
Seefried, Martina
Sonderforschungsbereich 643 Strategien der zellulären Immunintervention (Sprecher: Prof.Dr.Schuler)
Sell, Sabrina
Professur für Genetik
Sonnewald, Sophia PD Dr.
Lehrstuhl für Biochemie
Winkler, Thomas Prof. Dr.
Professur für Genetik


How to cite

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://dx.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.

BibTeX: 

Last updated on 2018-07-08 at 23:03