BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2023 Aug 17

PMID 37587835

Authors

Achia Khatun

Xiaopeng Wu

Fu Qi

Kexin Gai

Arjun Kharel

Matthew R Kudek

Lisa Fraser

Ashley Ceicko

Moujtaba Y Kasmani

Amber Majnik

Robert Burns

Yi-Guang Chen

Nita Salzman

Elizabeth J Taparowsky

Dayu Fang

Calvin B Williams

Weiguo Cui

Affiliations

Soon will be listed here.

Abstract

Regulatory T (Treg) cells are inevitable to prevent deleterious immune responses to self and commensal microorganisms. Treg function requires continuous expression of the transcription factor (TF) FOXP3 and is divided into two major subsets: resting (rTregs) and activated (aTregs). Continuous T cell receptor (TCR) signaling plays a vital role in the differentiation of aTregs from their resting state, and in their immune homeostasis. The process by which Tregs differentiate, adapt tissue specificity, and maintain stable phenotypic expression at the transcriptional level is still inconclusivei. In this work, the role of BATF is investigated, which is induced in response to TCR stimulation in naïve T cells and during aTreg differentiation. Mice lacking BATF in Tregs developed multiorgan autoimmune pathology. As a transcriptional regulator, BATF is required for Treg differentiation, homeostasis, and stabilization of FOXP3 expression in different lymphoid and non-lymphoid tissues. Epigenetically, BATF showed direct regulation of Treg-specific genes involved in differentiation, maturation, and tissue accumulation. Most importantly, FOXP3 expression and Treg stability require continuous BATF expression in Tregs, as it regulates demethylation and accessibility of the CNS2 region of the Foxp3 locus. Considering its role in Treg stability, BATF should be considered an important therapeutic target in autoimmune disease.

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