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Title

Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system
Authors
Prinz, Marco
Schmidt, Hauke
Mildner, Alexander
Knobeloch, Klaus-Peter
Hanisch, Uwe-Karsten
Raasch, Jenni
Merkler, Doron
Detje, Claudia
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Published in Immunity. 2008, vol. 28, no. 5, p. 675-686
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.
Keywords 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
Identifiers
PMID: 18424188
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Other version: http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=272197&_user=9565874&_pii=S107476130800126X&_check=y&_ori...
Structures
Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group La Sclérose en plaques (908)
Citation
(ISO format) 		PRINZ, Marco et al. Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. In: Immunity, 2008, vol. 28, n° 5, p. 675-686. doi: 10.1016/j.immuni.2008.03.011 https://archive-ouverte.unige.ch/unige:19115

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Deposited on : 2012-03-27

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