2022 Fiscal Year Annual Research Report
Invesitgation of Eomes+ Th cells: a pathogenic population controlling neuroinflammation during secondary progressive multiple sclerosis
| Project/Area Number |
20K07775
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
Raveney Benjamin 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 免疫研究部, 科研費研究員 (70795385)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Autoimmunity / Multiple sclerosis / Biomarker / T helper cells |
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| Outline of Annual Research Achievements |
Patients with the relapsing-remitting form of autoimmune disease multiple sclerosis (MS), often transition into a chronic progressive form (secondary progressive MS, SPMS). SPMS pathogenesis remains poorly understood with diagnosis based entirely on retrospective clinical monitoring. We have studied the role of Eomes-expressing CD4+ T cells (Eomes+ Th cells) in SPMS.
Objective 1: Direct isolation of Eomes+ Th cells is challenged by Eomes expression being intracellular, preventing live cell sorting. Using flow cytometry, we identified a number of surface molecules on Eomes+ Th cells linked to the function of these cells. As these molecules are cell surface-expressed, we have now been able to conduct cell sorting by flow cytometry. Th cells from peripheral blood and the CNS autopsy samples from SPMS have been characterised by TcR repertoire sequencing, indicating oligoclonal expansion with further analysis of gene expression to discern key functional properties underway.
Objective 2: We examined the level of Eomes+ Th cells in patients commencing treatment with a newly approved drug for SPMS that targets immune cells. By comparison with effectiveness of this treatment, we have additional evidence for the association of Eomes+ Th cells as pathogenic Th cells driving SPMS.
Objective 3. To examine the function of Eomes+ Th cells, we have compared the cytotoxic properties of circulating Th cells from peripheral blood in patient with SPMS and healthy control volunteers, and have been able to demonstrate an increase in cytotoxic potential of Eomes+ Th cells in SPMS.
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