The direct and indirect regulation of follicular T helper cell differentiation in inflammation and cancer

Follicular T helper (Tfh) cells play important roles in facilitating B‐cell differentiation and inducing the antibody response in humoral immunity and immune‐associated inflammatory diseases, including infections, autoimmune diseases, and cancers. However, Tfh cell differentiation is mainly achieved...

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Bibliographic Details
Published in:Journal of cellular physiology 2021-08, Vol.236 (8), p.5466-5480
Main Authors: Cao, Yejin, Dong, Lin, He, Ying, Hu, Xuelian, Hou, Yueru, Dong, Yingjie, Yang, Qiuli, Bi, Yujing, Liu, Guangwei
Format: Article
Language:English
Subjects:
Antibodies
Antibody response
Antigen-presenting cells
Antigens
Autoimmune diseases
B cells
Cancer
CD4 antigen
Cell differentiation
Cytokines
dendritic cells
Differentiation (biology)
follicular T helper cells
Gene regulation
Helper cells
Humoral immunity
infectious diseases
Inflammatory diseases
Lymphocytes
Lymphocytes T
Metabolism
T‐cell differentiation
T‐cell function
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Summary:Follicular T helper (Tfh) cells play important roles in facilitating B‐cell differentiation and inducing the antibody response in humoral immunity and immune‐associated inflammatory diseases, including infections, autoimmune diseases, and cancers. However, Tfh cell differentiation is mainly achieved through self‐directed differentiation regulation and the indirect regulation mechanism of antigen‐presenting cells (APCs). During the direct intrinsic differentiation of naïve CD4+ T cells into Tfh cells, Bcl‐6, as the characteristic transcription factor, plays the core role of transcriptional regulation. APCs indirectly drive Tfh cell differentiation mainly by changing cytokine secretion mechanisms. Altered metabolic signaling is also critically involved in Tfh cell differentiation. This review summarizes the recent progress in understanding the direct and indirect regulatory signals and metabolic mechanisms of Tfh cell differentiation and function in immune‐associated diseases. The process of naïve CD4+ T cells differentiating into follicular T helper (Tfh) cells and inducing the formation of germinal centers (GCs). Naïve CD4+ T cells differentiate into pre‐Tfh cells under the activation of dendritic cells (DCs). The pre‐Tfh cells migrate to the T‐B bounder and combine with activated B cells to further differentiate into GC‐Tfh cells. GC‐Tfh cells induce the maturation of GC‐B cells to form GCs.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.30263