EAE_CD4IFNGcKO_CD3

Experimental autoimmune encephalomyelitis (EAE) is the most widely used rodent model for multiple sclerosis. Interferon-? (IFN-?) 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-? and Tregs during the disease. Here we show that IFN-? 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-? stimulation during EAE. Loss of IFN-? signaling in Tregs and of T cell-derived IFN-? 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-? for Th1-Treg polarization in inflamed brain to ameliorate EAE. Overall design: EAE was induced into Ifng fl/fl and CD4-Cre/ Ifng fl/fl mice. CD3+ cells were isolated from the brain of the EAE-induced mice at peak of disease, and single cell RNA-seq was performed.