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

ABSTRACT: 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?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?92 spontaneously accumulated T(FH) 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 T(FH) differentiation and establish PHLPP2 as an important mediator of their function in this process.

SUBMITTER: Kang SG 

PROVIDER: S-EPMC3740954 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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

Kang Seung Goo SG   Liu Wen-Hsien WH   Lu Peiwen P   Jin Hyun Yong HY   Lim Hyung W HW   Shepherd Jovan J   Fremgen Daniel D   Verdin Eric E   Oldstone Michael B A MB   Qi Hai H   Teijaro John R JR   Xiao Changchun C  

Nature immunology 20130630 8

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∼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∼92 spontaneously accumulated T(FH) cells and developed a fatal i  ...[more]

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