The microRNA cluster miR-1792 promotes T sub(FH) cell differentiation and represses subset-inappropriate gene expression

Follicular helper T cells (T sub(FH) cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for T sub(FH) cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-1792 was critical for robust differentiation and function of T sub(FH) cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-1792 restrained the expression of genes 'inappropriate' to the T sub(FH) cell subset, including the direct miR-1792 target Rora. Removal of one Rora allele partially 'rescued' the inappropriate gene signature in miR-1792-deficient T sub(FH) cells. Our results identify the miR-1792 cluster as a critical regulator of T cell-dependent antibody responses, T sub(FH) cell differentiation and the fidelity of the T sub(FH) cell gene-expression program.