Epigenetic regulation of B cells and its role in autoimmune pathogenesis

Fan Xiao; Ke Rui; Xiaofei Shi; Haijing Wu; Xiaoyan Cai; Kathy O Lui; Qianjin Lu; Esteban Ballestar; Jie Tian; Hejian Zou; Liwei Lu

doi:10.1038/s41423-022-00933-7

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

Cell Mol Immunol. 2022 Nov;19(11):1215-1234. doi: 10.1038/s41423-022-00933-7. Epub 2022 Oct 12.

Authors

Fan Xiao¹, Ke Rui², Xiaofei Shi³, Haijing Wu⁴, Xiaoyan Cai⁵, Kathy O Lui⁶, Qianjin Lu⁴, Esteban Ballestar^{7

8}, Jie Tian⁹, Hejian Zou¹⁰, Liwei Lu^{11

12}

Affiliations

¹ Department of Pathology, Shenzhen Institute of Research and Innovation and Shenzhen Hospital, The University of Hong Kong, Hong Kong; Chongqing International Institute for Immunology, Chongqing, China.
² Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
³ Department of Rheumatology and Immunology, The First Affiliated Hospital and School of Medicine, Henan University of Science and Technology, Luoyang, China.
⁴ Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
⁵ Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
⁶ Department of Chemical Pathology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
⁷ Epigenetics and Immune Disease Group, Josep Carreras Research Institute, Badalona, 08916, Barcelona, Spain.
⁸ Epigenetics in Inflammatory and Metabolic Diseases Laboratory, Health Science Center, East China Normal University, Shanghai, China.
⁹ Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. tianjie@ujs.edu.cn.
¹⁰ Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China. hjzou@fudan.edu.cn.
¹¹ Department of Pathology, Shenzhen Institute of Research and Innovation and Shenzhen Hospital, The University of Hong Kong, Hong Kong; Chongqing International Institute for Immunology, Chongqing, China. liweilu@hku.hk.
¹² Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong, China. liweilu@hku.hk.

Abstract

B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation in patients with various autoimmune disorders, progress in epigenetic research has revealed new mechanisms leading to B-cell hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate B-cell responses, and their dysregulation can contribute to the pathogenesis of autoimmune diseases. Patients with autoimmune diseases show epigenetic alterations that lead to the initiation and perpetuation of autoimmune inflammation. Moreover, many clinical and animal model studies have shown the promising potential of epigenetic therapies for patients. In this review, we present an up-to-date overview of epigenetic mechanisms with a focus on their roles in regulating functional B-cell subsets. Furthermore, we discuss epigenetic dysregulation in B cells and highlight its contribution to the development of autoimmune diseases. Based on clinical and preclinical evidence, we discuss novel epigenetic biomarkers and therapies for patients with autoimmune disorders.

Keywords: Autoimmune disease; B cells; Biomarker; Epigenetic regulation; Therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmune Diseases* / genetics
B-Lymphocytes
DNA Methylation / genetics
Epigenesis, Genetic*
RNA, Untranslated / genetics

Substances

RNA, Untranslated