Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital/Children's Hospital and Harvard Medical School, Boston, MA, United States.
Front Immunol. 2021 Mar 26;12:641013. doi: 10.3389/fimmu.2021.641013. eCollection 2021.
Balance of Tfh/Tfr cell is critically important for the maintenance of immune tolerance, as evidenced by the fact that T follicular helper (Tfh) cells are central to the autoantibodies generation through providing necessary help for germinal center (GC) B cells, whereas T follicular regulatory (Tfr) cells significantly inhibit autoimmune inflammation process through restraining Tfh cell responses. However, signals underlying the regulation of Tfh and Tfr cells are largely undefined. Regulatory B cells (Bregs) is a heterogeneous subpopulation of B cells with immunosuppressive function. Considerable advances have been made in their functions to produce anti-inflammatory cytokines and to regulate Th17, Th1, and Treg cells in autoimmune diseases. The recent identification of their correlations with dysregulated Tfr/Tfh cells and autoantibody production makes Bregs an important checkpoint in GC response. Bregs exert profound impacts on the differentiation, function, and distribution of Tfh and Tfr cells in the immune microenvironment. Thus, unraveling mechanistic information on Tfh-Breg and Tfr-Breg interactions will inspire novel implications for the establishment of homeostasis and prevention of autoantibodies in diverse diseases. This review summarizes the dysregulation of Tfh/Tfr cells in autoimmune diseases with a focus on the emerging role of Bregs in regulating the balance between Tfh and Tfr cells. The previously unsuspected crosstalk between Bregs and Tfh/Tfr cells will be beneficial to understand the cellular mechanisms of autoantibody production and evoke a revolution in immunotherapy for autoimmune diseases.
滤泡辅助性 T 细胞（Tfh）/调节性滤泡 T 细胞（Tfr）细胞平衡对于维持免疫耐受至关重要，事实上，Tfh 细胞通过为生发中心（GC）B 细胞提供必要的帮助而成为产生自身抗体的核心，而 Tfr 细胞则通过抑制 Tfh 细胞的反应显著抑制自身免疫炎症过程。然而，调节 Tfh 和 Tfr 细胞的信号在很大程度上尚不清楚。调节性 B 细胞（Bregs）是具有免疫抑制功能的 B 细胞的异质性亚群。在自身免疫性疾病中，它们产生抗炎细胞因子和调节 Th17、Th1 和 Treg 细胞的功能方面取得了相当大的进展。最近发现它们与失调的 Tfr/Tfh 细胞和自身抗体产生有关，这使得 Bregs 成为 GC 反应的一个重要检查点。Bregs 对免疫微环境中 Tfh 和 Tfr 细胞的分化、功能和分布产生深远影响。因此，揭示 Tfh-Breg 和 Tfr-Breg 相互作用的机制信息将为在多种疾病中建立稳态和预防自身抗体产生提供新的启示。本综述总结了自身免疫性疾病中 Tfh/Tfr 细胞的失调，并重点介绍了 Bregs 在调节 Tfh 和 Tfr 细胞平衡中的新作用。Bregs 和 Tfh/Tfr 细胞之间以前未被怀疑的串扰将有助于理解自身抗体产生的细胞机制，并引发自身免疫性疾病免疫治疗的革命。
