Elucidation of the mechanism of brain tissue-specific regulatory T cell induction

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19382
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Minako Ito 九州大学, 生体防御医学研究所, 准教授 (70793115)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 制御性T細胞

Outline of Final Research Achievements

Naive Tregs derived from spleen were activated and efficiently amplified by T cell receptor (TCR) stimulation in the presence of primary astrocytes. Furthermore, the addition of IL-33 and serotonin was able to confer some of the characteristics of brain Tregs, such as ST2, PPARγ, and serotonin receptor 7 (Htr7) expression. For example, brain Treg markers such as Gata3, Pparg, Il1rl1, Klrg1, Penk, and Htr7 were highly expressed in iB-Tregs. Furthermore, in a Parkinson's disease model, in which T cells are implicated in disease progression, iB-Tregs infiltrated the brain more readily than splenic Tregs and more effectively ameliorated pathological symptoms. These data contribute to our understanding of brain Treg development and indicate that iB-Tregs may be a potential therapeutic agent for inflammatory brain diseases.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

制御性T細胞は免疫応答を抑制する細胞であり、様々な炎症性疾患の治療法となりうるが、全身性の免疫抑制のために感染症やがんの拡大などのリスクが高まることが問題として挙げられる。本研究では脳組織に特化したTregを作製することができるため他の組織への影響が少なく、副作用を抑えた治療法につながる。脳に限らず、他の組織の支持細胞や誘導因子と共培養することで、様々な組織特異的なTregの誘導に応用できる可能性がある。