MicroRNAs of the miR-23~27~24 family coordinately regulate T follicular helper cell responses during allergic reaction and viral infection

Abstract

Abstract T Follicular helper (Tfh) cells are essential for forming geminal centers (GCs) and promoting protective humoral immunity. On the other hand, aberrant Tfh cell responses could also lead to the production of autoantibodies and the development of autoimmunity. To date, microRNAs (miRNAs) have emerged as key molecular players in regulating Tfh cell differentiation and homeostasis. Here, by using both lost-of-function and gain-of-function approaches, we show that loss of miR-23~27~24 clusters in T cells resulted in elevated frequencies of Tfh and GC B cells upon allergen challenge as well as during viral infection whereas T cell-specific overexpression of this miRNA family led to reduced Tfh cell responses. Interestingly, unlike our previously reported findings which showed that individual members of this miRNA family do not always work with each other in regulating other T cell lineages, we found that the entire miR-23~27~24 family coordinately control Tfh cell responses through targeting a network of genes that are critical for Tfh cell differentiation and function. Collectively, our results establish miR-23~27~24 clusters as important regulators in maintaining optimal Tfh cell responses and the resultant humoral immunity.