Elucidation of the significance of regulatory T cells in the chronic phase of cerebral infarction

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15667
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: ITO MINAKO 慶應義塾大学, 医学部(信濃町), 特別研究員(PD) (70793115)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 制御性T細胞 / 脳梗塞

Outline of Final Research Achievements

We analyzed the significance of the acquired immune system in the chronic phase of cerebral infarction. In humans and mouse models, the relationship between control of chronic inflammation and the cranial nervous system is poorly understood. We found that in the mouse brain two weeks or more after the onset of cerebral infarction, a large amount of T cells, especially regulatory T cells (Tregs), accumulated much more than in the acute phase. Brain Tregs infiltrated in CCL1- and CCL20-dependent manner, proliferated in TCR-recognition-, IL-2-, IL-33-, and serotonin-dependent manner, and exhibited phenotypes different from those of other tissue Tregs. This brain Tregs controlled astrocyte gliosis (astrogliosis) and nerve injury by expressing amphiregulin (Areg) involved in tissue repair.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

脳梗塞モデルマウスを用いて、脳梗塞慢性期には獲得免疫を担うリンパ球の一種である制御性T細胞（Tレグ）が大量に梗塞部位に集積し、神経修復過程を制御していることを発見した。この脳Tレグは他の組織に存在するTレグと異なり神経系に特徴的なセロトニン受容体を有しており、セロトニンによって増殖・活性化することがわかった。脳梗塞モデルマウスにセロトニンや脳内のセロトニンを増やす薬（抗うつ薬の一種）を投与したところ、脳Tレグが増加し神経症状が改善した。脳梗塞患者においても脳内セロトニンに作用する抗うつ薬が、脳梗塞の慢性期（リハビリ期）の治療に役立つことが期待される。