T follicular helper (Tfh) cells are essential for the formation of germinal centers (GCs) and the development of long-lived humoral immunity. Tfh cell differentiation is a multistep process driven by the balanced expression of key transcription factors that form a regulatory network in which small changes in gene expression determine the Tfh cell fate decision. Here, we review recent findings that have revealed that certain microRNAs act as important mediators within this network, with roles in tuning gene expression. We integrate these findings into the current understanding of the mechanisms governing T helper cell differentiation, and propose a model in which the establishment of Tfh cell identity is dependent on the differential expression and concerted action of distinct microRNAs and transcription factors.
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