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 through self-directed differentiation regulation and the indirect regulation mechanism of antigen-presenting cells (APCs). During the direct intrinsic differentiation of naive 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.

Automated summary

Follicular T helper (Tfh) cells are crucial for B-cell differentiation and immune responses in humoral immunity and immune-related inflammatory diseases. Tfh cell differentiation involves self-directed and APCs-driven mechanisms, with Bcl-6 as a key transcription factor. Metabolic signaling also plays a critical role in Tfh cell differentiation.