IFNβ secreted by microglia mediates clearance of myelin debris in CNS autoimmunity

小胶质细胞分泌的 IFNβ 介导中枢神经系统自身免疫中髓鞘碎片的清除

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作者:Magdalena Kocur, Reiner Schneider, Ann-Kathrin Pulm, Jens Bauer, Sonja Kropp, Michael Gliem, Jens Ingwersen, Norbert Goebels, Judith Alferink, Timour Prozorovski, Orhan Aktas, Stefanie Scheu

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.

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.

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