2020 Fiscal Year Research-status 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
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
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)
|
|---|
| Project Period (FY) |
2020-04-01 – 2022-03-31
|
| Keywords | neurodegeneration / microglia / multiple sclerosis |
|---|
| Outline of Annual Research Achievements |
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.
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Most of undergoing experiments and current results are reliable and reasonable according to the objective of this study. Now, the manuscript is preparing.
|
| Strategy for Future Research Activity |
1 To find out what are the possible antigens that are presented by microglia to stimulate Th cells accumulated in the central nervous system. Now, we already screened and selected some possible antigen for test.
2 The distribution of the possible antigens that are presented by microglia in intact and neurodegeneration CNS. We will use cutting-edge Lightsheet Z.1 and SmartLabel system to show the distribution in the whole brain.
3 Clinical benefit of interference of production of the possible antigens that are presented by microglia.
We will use specific inhibitor(s) or antibody to abolish the production or inhibit the binding to helper T cells.
|
| Causes of Carryover |
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.
|
