IFN-γ-induced Th1-Treg Polarization in Inflamed Brains Limits Exacerbation of Experimental Autoimmune Encephalomyelitis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2024 Nov 19

PMID 39560646

Authors

Masaaki Okamoto

Ayumi Kuratani

Daisuke Okuzaki

Naganori Kamiyama

Takashi Kobayashi

Miwa Sasai

Masahiro Yamamoto

Affiliations

Soon will be listed here.

Abstract

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 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-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 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-γ for Th1-Treg polarization in inflamed brain to ameliorate EAE.

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