The microRNA cluster miR-17~92 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- 17~92 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-17~92 restrained the expression of genes 'inappropriate' to the [T.sub.FH] cell subset, including the direct miR-17~92 target Rora. Removal of one Rora allele partially 'rescued' the inappropriate gene signature in miR-17~92-deficient [T.sub.FH] cells. Our results identify the miR-17~92 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.