Interactions between Th17 and CD8+ T cells in animal models of multiple sclerosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07433
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kindai University
• Principal Investigator: Sato Fumitaka 近畿大学, 医学部, 講師 (30779327)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 動物モデル / Th17細胞 / ピコルナウイルス科 / IgA

Outline of Final Research Achievements

Multiple sclerosis (MS) is an immune-mediated disease in the central nervous system (CNS). Although helper T (Th) 17 cells have been suggested to play pathogenic roles in MS, the precise pathomechanisms are unclear. We have used a viral model of MS, Theiler’s murine encephalomyelitis virus (TMEV) infection in mice, in which we can see infiltration of Th17 and CD8+ T cells in the CNS that resembles MS neuropathologically. In this study, using the viral model, we aimed to determine the pathogenesis of MS by treating mice with a Th17 modulator, curdlan. Compared with control mice, curdlan-treated mice had significantly less severe clinical signs with decreased levels of CD8+ T cells and granzyme B in the CNS. We also found lower levels of IgA deposition in the CNS demyelinating lesions in curdlan-treated mice. Since IgA-producing B cells have been detected in the CNS of MS patients, our findings suggest the novel interactions among Th17, CD8+ T-cell, and IgA responses in MS.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

近年の臨床・基礎研究より，多発性硬化症(MS)はヘルパーT(Th)17細胞が疾患の原因であると提唱されている。しかしながら，Th17細胞機能阻害薬はMS治験において十分な効果を認めていない。その原因として，MS病態にはTh17細胞だけでなく，CD8+T細胞や他の免疫反応が関与していると思われる。MS動物モデルを用いた本研究では，Th17細胞の増強が病態に影響を及ぼすとともに，CNS内でのCD8+T細胞やIgA抗体の動態も変化することを示した。Th17細胞－CD8+T細胞－IgA抗体間のコミュニケーションを報告した研究は極めて少なく，今後のMS治療法の確立に新しい光明を投じる可能性を示唆した。