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Publication : A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells.

First Author  Liu WH Year  2016
Journal  J Exp Med Volume  213
Issue  9 Pages  1901-19
PubMed ID  27481129 Mgi Jnum  J:236627
Mgi Id  MGI:5806693 Doi  10.1084/jem.20160204
Citation  Liu WH, et al. (2016) A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells. J Exp Med 213(9):1901-19
abstractText  MicroRNA (miRNA) deficiency impairs the generation of T follicular helper (Tfh) cells, but the contribution of individual miRNAs to this phenotype remains poorly understood. In this study, we performed deep sequencing analysis of miRNAs expressed in Tfh cells and identified a five-miRNA signature. Analyses of mutant mice deficient of these miRNAs revealed that miR-22 and miR-183/96/182 are dispensable, but miR-155 is essential for the generation and function of Tfh cells. miR-155 deficiency led to decreased proliferation specifically at the late stage of Tfh cell differentiation and reduced CD40 ligand (CD40L) expression on antigen-specific CD4(+) T cells. Mechanistically, miR-155 repressed the expression of Peli1, a ubiquitin ligase that promotes the degradation of the NF-kappaB family transcription factor c-Rel, which controls cellular proliferation and CD40L expression. Therefore, our study identifies a novel miR-155-Peli1-c-Rel pathway that specifically regulates Tfh cell generation and function.
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