title: Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system.
abstract: The action of type I interferons in the central nervous system (CNS) during autoimmunity is largely unknown. Here, we demonstrate elevated interferon beta concentrations in the CNS, but not blood, of mice with experimental autoimmune encephalomyelitis (EAE), a model for CNS autoimmunity. Furthermore, mice devoid of the broadly expressed type I IFN receptor (IFNAR) developed exacerbated clinical disease accompanied by a markedly higher inflammation, demyelination, and lethality without shifting the T helper 17 (Th17) or Th1 cell immune response. Whereas adoptive transfer of encephalitogenic T cells led to enhanced disease in Ifnar1(-/-) mice, newly created conditional mice with B or T lymphocyte-specific IFNAR ablation showed normal EAE. The engagement of IFNAR on neuroectodermal CNS cells had no protective effect. In contrast, absence of IFNAR on myeloid cells led to severe disease with an enhanced effector phase and increased lethality, indicating a distinct protective function of type I IFNs during autoimmune inflammation of the CNS.
authors.affiliation: Department of Neuropathology, University of Freiburg, D-79106 Freiburg, Germany. marco.prinz@uniklinik-freiburg.de
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Hauke
authors.initials: H
authors.lastname: Schmidt
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Knobeloch
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.forename: Jenni
authors.initials: J
authors.lastname: Raasch
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Claudia
authors.initials: C
authors.lastname: Detje
authors.forename: Ilona
authors.initials: I
authors.lastname: Gutcher
authors.forename: Jörg
authors.initials: J
authors.lastname: Mages
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D017628:Microglia / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000949:Histocompatibility Antigens Class II; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta