title: Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection.
abstract: During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8(+) T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso(-/-)) mice reduced CD8(+) T-cell function in the liver and resulted in virus persistence. Furthermore, Toso(-/-) DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection.
authors.affiliation: 1] Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany [2] Department of Molecular Medicine II, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany.
authors.forename: P A
authors.initials: PA
authors.lastname: Lang
authors.affiliation: 1] Department of Molecular Medicine II, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany [2] Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Meryk
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: A A
authors.initials: AA
authors.lastname: Pandyra
authors.affiliation: 1] Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, UHN, 620 University Avenue Toronto, Toronto, ON, Canada M5G 2C1 [2] Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität Munich, Munich 81675, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Brenner
authors.affiliation: Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, UHN, 620 University Avenue Toronto, Toronto, ON, Canada M5G 2C1.
authors.forename: A
authors.initials: A
authors.lastname: Brüstle
authors.affiliation: 1] Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany [2] Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: H C
authors.identifier: 0000000246744983
authors.initials: HC
authors.lastname: Xu
authors.affiliation: 1] Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany [2] Department of Physiology I, University of Tuebingen, Gmelinstr. 5, Tuebingen 72076, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Merches
authors.affiliation: Department of Physiology I, University of Tuebingen, Gmelinstr. 5, Tuebingen 72076, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: V
authors.identifier: 0000000235847530
authors.initials: V
authors.lastname: Khairnar
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Funkner
authors.affiliation: Primary Immunodeficiency Clinic, Medical Outpatient Division and Immunodeficiency Lab, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Recher
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Shaabani
authors.affiliation: Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, UHN, 620 University Avenue Toronto, Toronto, ON, Canada M5G 2C1.
authors.forename: G S
authors.initials: GS
authors.lastname: Duncan
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Duhan
authors.affiliation: Department of Dermatology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Homey
authors.affiliation: Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, UHN, 620 University Avenue Toronto, Toronto, ON, Canada M5G 2C1.
authors.forename: P S
authors.initials: PS
authors.lastname: Ohashi
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Institute of Molecular Immunology, Technische Universität Munich, Munich 81675, Germany.
authors.forename: P A
authors.initials: PA
authors.lastname: Knolle
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Honke
authors.affiliation: Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, UHN, 620 University Avenue Toronto, Toronto, ON, Canada M5G 2C1.
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: 1] Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany [2] Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
authors.forename: K S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats
chemical_list: D002352:Carrier Proteins; C499656:Fcmr protein, mouse; D008565:Membrane Proteins