MicroRNA-mediated regulation of T follicular helper and T follicular regulatory cell identity

T follicular helper (Tfh) cells are critical mediators of germinal center (GC) formation and essential for potent humoral immunity. In contrast, T follicular regulatory (Tfr) cells, which share characteristics of both stimulatory Tfh cells and suppressive regulatory T (Treg) cells, restrain excessive GC responses. Tfh cell differentiation is a multistep process that involves continuous interaction with antigen-presenting cells, co-stimulatory signals, an appropriate cytokine milieu, and directed migration toward distinct microanatomical structures. These processes are under the control of several intrinsic and extrinsic regulatory layers that further undergo fine-tuning by post-transcriptional mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that have been recognized as important post-transcriptional regulators. miRNAs are particularly critical for Tfh cell generation, as the differentiation of these cells is completely blocked in the absence of mature miRNAs in vivo. Here, we discuss how miRNAs regulate various aspects of Tfh and Tfr cell differentiation and function and how miRNAs thus shape the identity of these cells.