Chunhong Zhu; Xiaoying Ni; Jiangming Xu; Hao Wang; Hongqiang Shen
Abstract
The balance between follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) is crucial for maintaining immune tolerance. Tfh cells are key in producing autoantibodies by providing essential help to germinal center (GC) B cells, while Tfr cells prevent autoimmune inflammatory processes ...
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The balance between follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) is crucial for maintaining immune tolerance. Tfh cells are key in producing autoantibodies by providing essential help to germinal center (GC) B cells, while Tfr cells prevent autoimmune inflammatory processes by controling Tfh responses. However, the signals that regulate Tfh and Tfr cells are largely unknown. Due to dysregulated Tfr/Tfh balance and autoantibody production, regulatory B cells (Bregs) have emerged as a key checkpoint in the GC response. Bregs are B cells with immunosuppressive capabilities. Significant advancements have been made in understanding the roles of Bregs, particularly their capacity to produce cytokines with anti-inflammatory properties and regulate Th17, Th1, and regulatory T cells (Tregs) in the context of autoimmune conditions. Bregs also play a pivotal role in shaping the development, regulation, and localization of Tfh and Tfr cells within the immune environment. Consequently, gaining mechanistic knowledge about the interactions between Tfh-Bregs and Tfr-Bregs has the potential to establish homeostasis and suppress the development of autoantibodies in a various disorders. Within the context of autoimmune disorders, this article provides a concise summary of the dysregulation of Tfh/Tfr, highlighting the critical role of Bregs in regulating this balance. The previously unrecognized interplay between Bregs and Tfh/Tfr cells will serve as an essential basis for the comprehension and management of autoimmune illnesses. It also promises to offer invaluable knowledge of the biological mechanisms of autoantibody synthesis.
Sara Iranparast; Farhad Seif; Sanaz Tayebi; Farhad Abolnezhadian; Moosa Sharifat; Alireza Fazaeli; Neda Roshanravan; Azam Samei; Sholeh Khajoei
Abstract
Follicular helper T (TFH) cells are a subset of effector CD4+ T cells that support the differentiation of antigen-specific B cells in the germinal center. TFH cells are distinct from other established CD4+ T cell subsets and possess a list of transcription factors, including BCL6, IRF4, c-Maf, Batf, ...
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Follicular helper T (TFH) cells are a subset of effector CD4+ T cells that support the differentiation of antigen-specific B cells in the germinal center. TFH cells are distinct from other established CD4+ T cell subsets and possess a list of transcription factors, including BCL6, IRF4, c-Maf, Batf, NFAT1-2, and STAT3. The mentioned factors direct several activities such as cell differentiation, migration to the follicles, cell-to-cell interaction, as well as cell programming. Given that TFH cells are essential for the germinal center formation, affinity maturation and the development of most high-affinity antibodies. TFH cells may play crucial roles in different pathologic conditions, particularly autoimmune diseases. However, the mechanisms that cause functional differences of TFH cell responses are not exactly defined. In this review first the immunological profile of TFH cells will be discussed then attempts will be made to give a broad picture on the role of this key subset of T cells in autoimmune diseases.
