MicroRNAs of the miR-17~92 family are critical regulators of T(FH) differentiation

T follicular helper (T(FH)) cells provide critical help to B cells during humoral immune responses. Here we report that mice with T cell-specific deletion of miR-17~92 family miRNAs (tKO mice) exhibited severely compromised T(FH) differentiation, germinal center formation, antibody responses, and failed to control chronic virus infection. Conversely, T cell-specific miR-17~92 transgenic mice spontaneously accumulated T(FH) cells and developed fatal immunopathology. Mechanistically, miR-17~92 family miRNAs control CD4(+) T cell migration into B cell follicles by regulating ICOS-PI3K signaling intensity through suppressing the expression of the Akt phosphatase Phlpp2. These findings demonstrate that miR-17~92 family microRNAs play an essential role in T(FH) differentiation and establish Phlpp2 as an important mediator of their function in this process.