Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system

Article Article scientifique Article Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system eng 2008 author Prinz Marco author Schmidt Hauke author Mildner Alexander author Knobeloch Klaus-Peter author Hanisch Uwe-Karsten author Raasch Jenni author Merkler Doron 735735 author Detje Claudia author Gutcher Ilona author Mages Jorg author Lang Roland author Martin Roland Fraser 24615 author Gold Ralf author Becher Burkhard author Bruck Wolfgang author Kalinke Ulrich 675-686 10.1016/j.immuni.2008.03.011 18424188 1074-7613 http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=272197&_user=9565874&_pii=S107476130800126X&_check=y&_origin=article&_zone=toolbar&_coverDate=16-May-2008&view=c&originContentFamily=serial&wchp=dGLbVlV-zSkWA&md5=27693706591ea059a660c210a6dfe815/1-s2.0-S107476130800126X-main.pdf 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. Adoptive Transfer Animals *Autoimmunity B-Lymphocytes/immunology Brain/immunology/metabolism Central Nervous System/*immunology/metabolism Disease Progression Encephalomyelitis, Autoimmune, Experimental/*immunology/metabolism Female Histocompatibility Antigens Class II/metabolism Interferon-beta/immunology/*metabolism Mice Mice, Mutant Strains Microglia/metabolism Myeloid Cells/*immunology/metabolism Receptor, Interferon alpha-beta/immunology/*metabolism Signal Transduction Spinal Cord/immunology/metabolism T-Lymphocyte Subsets/*immunology/metabolism Transcription, Genetic Dewey 616.07 137 Département de pathologie et immunologie 21F false 565 La Sclérose en plaques 908 Immunity 28 5 4e1e9802-ba0d-40c5-8a71-81bad51e4632 Article Restricted file1.pdf 2104950 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system	Immunity			2008	581	0

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Martin, Roland Fraser