title: Siglec-H protects from virus-triggered severe systemic autoimmunity.
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-α, in vitro and that Siglec-H knockout (KO) mice produce more IFN-α 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.
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Schmitt
authors.affiliation: Nikolaus-Fiebiger-Zentrum, Division of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Sabrina
authors.identifier: 0000-0002-4584-2733
authors.initials: S
authors.lastname: Sell
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Koch
authors.affiliation: Nikolaus-Fiebiger-Zentrum, Division of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Martina
authors.identifier: 0000-0002-9870-3534
authors.initials: M
authors.lastname: Seefried
authors.affiliation: Division of Biochemistry, Department of Biology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Sophia
authors.identifier: 0000-0002-9185-6255
authors.initials: S
authors.lastname: Sonnewald
authors.affiliation: Department of Nephropathology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Christoph
authors.identifier: 0000-0002-6803-4755
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Nikolaus-Fiebiger-Zentrum, Division of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany lars.nitschke@fau.de thomas.winkler@fau.de.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Winkler
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany lars.nitschke@fau.de thomas.winkler@fau.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; D037102:Lectins; D011956:Receptors, Cell Surface; C510552:Siglech protein, mouse