大阪大学微生物病研究所 岡本将明特任研究員（研究当時）、山本雅裕教授（免疫学フロンティア研究センター、感染症総合教育研究拠点兼任）らの研究グループは、多発性硬化症の動物モデルであるEAE発症マウスにおいて、IFN-γの刺激によってTregからTh1-Tregへの分化が誘導され、このTh1-Tregが病変部に集積することで病気の悪化を抑えていることを明らかにしました。
本研究成果は、米国科学誌「Proceedings of the National Academy of Sciences of the United States of America （米国科学アカデミー紀要）」（オンライン）で2024年11月19日に公開されました。

【 詳細はこちら(ResOU) 】

Experimental autoimmune encephalomyelitis (EAE) is the most widely used rodent model for multiple sclerosis. Interferon-γ (IFN-γ) and regulatory T cells (Tregs) are individually well known to play beneficial roles in amelioration of EAE. However, little is known about the relationship between IFN-γ and Tregs during the disease. Here we show that IFN-γ polarizes Tregs into Th1-type Tregs (Th1-Tregs) to recover from EAE. Single-cell RNA sequencing analysis revealed that brain Tregs showed signs of IFN-γ stimulation during EAE. Loss of IFN-γ signaling in Tregs and of T cell-derived IFN-γ impaired the Th1-Treg polarization and worsened the disease. Moreover, selective ablation of Th1-Tregs using an intersectional genetic method promoted pro-inflammatory features of macrophages in the inflamed brains and exacerbated the EAE. Taken together, our study highlights a critical role of T cell-derived IFN-γ for Th1-Treg polarization in inflamed brain to ameliorate EAE.

Title：“IFN-γ-induced Th1-Treg polarization in inflamed brains limits exacerbation of experimental autoimmune encephalomyelitis”
Authors：Masaaki Okamoto, Ayumi Kuratani, Daisuke Okuzaki, Naganori Kamiyama, Takashi Kobayashi, Miwa Sasai and Masahiro Yamamoto

DOI: 10.1073/pnas. 2401692121