| 研究実績の概要 |
In this study, we revealed that disease-associated microglia emerged under chronic inflammation act as a pathogenic nexus in immune cell-mediated neurodegeneration via the secretion of type I interferons inducing upregulation of MHC class II and antigen presentation and prolactin producing in antigen-presenting cells which leads in turn to Eomes expression in Th cells. Strikingly, a retrotransposon protein, ORF1, encoded by long interspersed nuclear element-1 (L1), stimulated such T cells in an MHC-class II restricted manner. Furthermore, blockade of IFN-I signals and activation of retroelements attenuated the late phase of EAE in in vivo experiments. We therefore suggest that neuroimmune interactions play an intrinsic role in the transition to Eomes+ Th cell-associated neurodegeneration.
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