MicroRNAs of the miR-17∼92 family are critical regulators of TFH differentiation

초록

Follicular helper T cells (T-FH cells) provide critical help to B cells during humoral immune responses. Here we report that mice with T cell-specific deletion of the miR-17 similar to 92 family of microRNAs (miRNAs) had substantially compromised T-FH differentiation, germinal-center formation and antibody responses and failed to control chronic viral infection. Conversely, mice with T cell-specific expression of a transgene encoding miR-17 similar to 92 spontaneously accumulated T-FH cells and developed a fatal immunopathology. Mechanistically, the miR-17 similar to 92 family controlled the migration of CD4(+) T cells into B cell follicles by regulating signaling intensity from the inducible costimulator ICOS and kinase PI(3) K by suppressing expression of the phosphatase PHLPP2. Our findings demonstrate an essential role for the miR-17 similar to 92 family in T-FH differentiation and establish PHLPP2 as an important mediator of their function in this process.

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