2021 Fiscal Year Annual Research Report
Analysis on detrimental interplay between pathogenic helper T cells, inflammatory antigen-presenting cells and disease-associated microglia in chronic pathogenesis of multiple sclerosis
| Project/Area Number |
20K16294
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
張 晨陽 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40768363)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | neurodegeneration / multiple sclerosis |
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| Outline of Annual Research Achievements |
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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