IFN-γ-induced Th1-Treg polarization in inflamed brains limits exacerbation of experimental autoimmune encephalomyelitis

• 成果类型: Article
• 署名作者: Okamoto, Masaaki; Kuratani, Ayumi; Okuzaki, Daisuke; Kamiyama, Naganori; Kobayashi, Takashi; Sasai, Miwa; Yamamoto, Masahiro
• 署名单位: University of Osaka; University of Osaka; University of Osaka; Oita University; Oita University; University of Osaka
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10181
• DOI: 10.1073/pnas.2401692121
• 发表日期: 2024-11-26
• 关键词: regulatory t-cells; experimental allergic encephalomyelitis; interferon-gamma; th17 cells; differentiation; inflammation; macrophages; effector; roles; bet

摘要

Experimental autoimmune encephalomyelitis (EAE) is the most widely used rodent model for multiple sclerosis. Interferon-gamma (IFN-gamma) 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-gamma and Tregs during the disease. Here, we show that IFN-gamma polarizes Tregs into T helper 1 (Th1)-type Tregs (Th1- Tregs) to recover from EAE. Single- cell RNA sequencing analysis revealed that brain Tregs showed signs of IFN-gamma stimulation during EAE. Loss of IFN-gamma signaling in Tregs and of T cell- derived IFN-gamma impaired the Th1-Treg polarization and worsened the disease. Moreover, selective ablation of Th1-Tregs using an intersectional genetic method promoted proinflammatory features of macrophages in the inflamed brains and exacerbated the EAE. Taken together, our study highlights a critical role of T cell- derived IFN-gamma for Th1-Treg polarization in inflamed brain to ameliorate EAE.