title: IFNβ secreted by microglia mediates clearance of myelin debris in CNS autoimmunity.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS) leading to progressive neurological disability. Interferon β (IFNβ) represents a standard treatment for relapsing-remitting MS and exogenous administration of IFNβ exhibits protective effects in experimentally induced CNS autoimmunity. Also, genetic deletion of IFNβ in mice leads to an aggravation of disease symptoms in the MS model of experimental autoimmune encephalomyelitis (EAE). However, neither the underlying mechanisms mediating the beneficial effects nor the cellular source of IFNβ have been fully elucidated.
  
  
  RESULTS
  In this report, a subpopulation of activated microglia was identified as the major producers of IFNβ in the CNS at the peak of EAE using an IFNβ-fluorescence reporter mouse model. These IFNβ expressing microglia specifically localized to active CNS lesions and were associated with myelin debris in demyelinated cerebellar organotypic slice cultures (OSCs). In response to IFNβ microglia showed an enhanced capacity to phagocytose myelin in vitro and up-regulated the expression of phagocytosis-associated genes. IFNβ treatment was further sufficient to stimulate association of microglia with myelin debris in OSCs. Moreover, IFNβ-producing microglia mediated an enhanced removal of myelin debris when co-transplanted onto demyelinated OSCs as compared to IFNβ non-producing microglia.
  
  
  CONCLUSIONS
  These data identify activated microglia as the major producers of protective IFNβ at the peak of EAE and as orchestrators of IFNβ-induced clearance of myelin debris.
authors: Magdalena
authors: M
authors: Kocur
authors: Reiner
authors: R
authors: Schneider
authors: Ann-Kathrin
authors: AK
authors: Pulm
authors: Jens
authors: J
authors: Bauer
authors: Sonja
authors: S
authors: Kropp
authors: Michael
authors: M
authors: Gliem
authors: Jens
authors: J
authors: Ingwersen
authors: Norbert
authors: N
authors: Goebels
authors: Judith
authors: J
authors: Alferink
authors: Timour
authors: T
authors: Prozorovski
authors: Orhan
authors: O
authors: Aktas
authors: Stefanie
authors: S
authors: Scheu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D016899:Interferon-beta / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D009924:Organ Culture Techniques; D010587:Phagocytosis / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D016899:Interferon-beta