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Nat Immunol. 2013 Aug;14(8):840-8. doi: 10.1038/ni.2642. Epub 2013 Jun 30.

The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression.

Author information

1
Department of Microbiology & Immunology, Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, California, USA.

Abstract

Follicular helper T cells (TFH 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 TFH 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 TFH 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 TFH 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 TFH cells. Our results identify the miR-17∼92 cluster as a critical regulator of T cell-dependent antibody responses, TFH cell differentiation and the fidelity of the TFH cell gene-expression program.

PMID:
23812098
PMCID:
PMC3720769
DOI:
10.1038/ni.2642
[Indexed for MEDLINE]
Free PMC Article
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