| 研究実績の概要 |
According to the objective of this study, that is, to clarify the cellular interplay between pathogenic CD4+ Th cells, ectopic PRL producing cells and disease-associated microglia in chronic pathogenesis of multiple sclerosis, our current results revealed that microglia played a pivotal role for Eomes+ Th cell-mediated neurodegeneration.
1) Primed microglia under chronic inflammation secreted type I interferon (IFN-I) that induced PRL in antigen-presenting cells and following Eomes expression in Th cells. And interfering activation of microglia attenuates EAE disease.Moreover, blockade of IFN-I signals brings clinical benefits in late EAE.
2) Microglia upregulates surface MHC class II (MHC II) expression. By using GeneChip and single-cell analysis,
we found profoundly gene expression changes during EAE.
3) Intriguingly, we found some proteins as prototypic antigens that stimulate Th cells accumulated in the central nervous system. Such miscellaneous CNS antigens may act as trigger for pathogenesis in late EAE disease
Collectively, our current study highlighted that chronic inflammation in the CNS provoked a functional fluctuation in microglia and immune cells, mutual exchange of which form a previously unappreciated vicious network that leads to neurodegeneration.
|
| 次年度使用額が生じた理由 |
The amount will be used for 1)animal and stuff;
2) manuscript preparation;
3)moreover, due to Covid-19, conferences include domestic and oversea were cancelled. This year, they are probably to attend.
|
