Faculty Collaboration Database

BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology. Adv Sci (Weinh) 2023 Oct;10(28):e2206692

Date

08/17/2023

Pubmed ID

37587835

Pubmed Central ID

PMC10558681

DOI

10.1002/advs.202206692

Scopus ID

2-s2.0-85168114370 (requires institutional sign-in at Scopus site)   2 Citations

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.

Author List

Khatun A, Wu X, Qi F, Gai K, Kharel A, Kudek MR, Fraser L, Ceicko A, Kasmani MY, Majnik A, Burns R, Chen YG, Salzman N, Taparowsky EJ, Fang D, Williams CB, Cui W

Authors

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Matthew Kudek MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Autoimmune Diseases
Cell Differentiation
Forkhead Transcription Factors
Mice
Receptors, Antigen, T-Cell
T-Lymphocytes, Regulatory