Elucidation of neurodegenerative pathology using regulatory gene program of T cells in immune neurological diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03562
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kobe University
• Principal Investigator: CHIHARA NORIO 神戸大学, 医学部附属病院, 特命講師 (70781821)
• Co-Investigator(Kenkyū-buntansha): 松本 理器 神戸大学, 医学研究科, 教授 (00378754) ; 古屋敷 智之 神戸大学, 医学研究科, 教授 (20362478)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多発性硬化症 / 個別化医療 / PD-1 / c-Maf / 共抑制性受容体

Outline of Final Research Achievements

Global gene expression analysis of genes co-expressed with Programmed cell death 1(PD-1) in PD-1-expressing CD8+ T cells reflecting a favorable course in patients with multiple sclerosis (MS) identified a gene program that includes a group of co-inhibitory genes program common to multiple T cell dysfunctional states. We found that this gene program in T cells is regulated by the transcription factor c-Maf. c-Maf induced gene and protein expression of co-inhibitory receptors such as PD-1 in human CD8+ T cells and promoted the production of the immunosuppressive cytokine IL-10. Furthermore, c-Maf-expressing CD8+ T cells suppressed the survival of allogeneic CD4+ T cells, which are considered pathogenic in MS, demonstrating that c-Maf-expressing CD8+ T cells have immunomodulatory properties.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、MS患者の病勢や治療反応性を反映したCD8陽性T細胞亜分画を新たに同定し、その免疫制御機能を発見した。このT細胞亜分画は進行性の良好な経過を反映した新たなバイオマーカーとして用いることができるのみならず、そのPD-1と共発現する遺伝子群が神経障害の進行する患者の予防する新規治療標的となる可能性があり、今後さらに検討を行ってゆく。