Regulation of Multiple Sclerosis Pathogenesis by Gut Environment-Induced T cells.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19526
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Kadowaki Atsushi 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, 研究生 (00751025)
• Research Collaborator: SAGA Ryoko ; LIN Youwei ; SATO Wakiro ; YAMAMURA Takashi
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 多発性硬化症(MS) / 二次進行型MS / 腸内細菌 / 腸管ホーミングレセプターCCR9 / CD4+メモリーT細胞

Outline of Final Research Achievements

Although alterations in gut microbiota in the pathogenesis of MS have recently been highlighted, the mechanism linking the altered gut environment with the remote central nervous system (CNS) pathology remains unclear. We focused on the gut-homing receptor CCR9+ CD4+ memory T cells (CCR9+Tm). We showed that CCR9+Tm cells, of which the frequency is influenced by normal aging and the gut microbiota, were reduced and that their immune-regulatory phenotype were deviated to inflammatory Th17 phenotype in patients with SPMS. CCR9+ Tm cells, which upregulated LAG-3 in the CSF, expressed high levels of C-MAF, and produced disease-protective cytokines (IL-4/IL-10). Thus, it appears that gut tropic CCR9+ Tm cells may play a critical role in the natural regulation of CNS autoimmunity, and that their reduced frequency and altered phenotype may at least partly account for the pathogenesis of SPMS. CCR9+ Tm cells may serve as potential diagnostic markers and therapeutic targets of SPMS.

Free Research Field

神経免疫