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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02050

Bach2 deficiency leads to spontaneous expansion of IL-4-producing T follicular helper cells and autoimmunity

 Chuanxin Huang1, 2*, Heng Zhang1, 2, Qianwen Hu1, 2,  Min Zhang3, Fang Yang2,  Cheng Peng2 and  Zhen Zhang3
  • 1School of Medicine, Shanghai Jiao Tong University, China
  • 2Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, China
  • 3Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, China

The transcription factor Bach2 is a susceptible gene for numerous autoimmune diseases including systemic lupus erythematosus. Bach2-/- mice can develop a lupus-like autoimmune disease. However, the exact cellular and molecular mechanisms via which Bach2 protects the hosts from developing autoimmunity remains incompletely understood. Here, we report that Bach2 ablation on T cells, but not B cells, resulted in humoral autoimmunity, and this was associated with expansion of T follicular helper (Tfh) cells and abnormal germinal centers. Bach2 was down-regulated in Tfh cells, and directly suppressed by the Tfh-defining transcription factor BCL6. Mechanistically, Bach2 directly suppresses the transcription of Cxcr5 and c-Maf, two key regulators of Tfh cell differentiation. Bach2-deficient Tfh cells were skewed towards IL-4-producing subset, which induced IgG1 and IgE isotype switching of B-cells. Heterozygous Bcl6 deficiency reduced the formation of germinal center and autoantibodies, and ameliorated the pathology in Bach2-deficient mice. Our findings identify Bach2 as a crucial negative regulator of Tfh cells at steady state, and prove that Bach2 controls autoimmunity in part by restraining accumulation of pathogenic Tfh cells.

Keywords: BACH2, T follicular helper cells, IL-4, Autoimmunity, BCL6

Received: 20 May 2019; Accepted: 14 Aug 2019.

Edited by:

Yun-Cai Liu, Tsinghua University, China

Reviewed by:

Xindong Liu, Army Medical University, China
Youn Soo Choi, Seoul National University College of Medicine, South Korea  

Copyright: © 2019 Huang, Zhang, Hu, Zhang, Yang, Peng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Chuanxin Huang, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China, huangcx@shsmu.edu.cn