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

SG Kang, WH Liu, P Lu, HY Jin, HW Lim… - Nature …, 2013 - nature.com
SG Kang, WH Liu, P Lu, HY Jin, HW Lim, J Shepherd, D Fremgen, E Verdin, MBA Oldstone…
Nature immunology, 2013nature.com
Follicular helper T cells (TFH 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∼ 92 family
of microRNAs (miRNAs) had substantially compromised TFH 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∼ 92 spontaneously
accumulated TFH cells and developed a fatal immunopathology. Mechanistically, the miR …
Abstract
Follicular helper T cells (TFH 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∼92 family of microRNAs (miRNAs) had substantially compromised TFH 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∼92 spontaneously accumulated TFH cells and developed a fatal immunopathology. Mechanistically, the miR-17∼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∼92 family in TFH differentiation and establish PHLPP2 as an important mediator of their function in this process.
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