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J Exp Med. 2016 Aug 22;213(9):1901-19. doi: 10.1084/jem.20160204. Epub 2016 Aug 1.

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

Author information

1
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361005, China cxiao@scripps.edu whliu@xmu.edu.cn guofu@xmu.edu.cn.
2
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 Division of Biomedical Convergence/Institute of Bioscience and Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
3
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
4
Division of Biological Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
5
Department of Microbiology, Immunology, and Molecular Genetics, Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095.
6
Department of Ophthalmology/Kresge Eye Institute, School of Medicine, Wayne State University, Detroit, MI 48202 Department of Anatomy and Cell Biology, School of Medicine, Wayne State University, Detroit, MI 48202.
7
Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037.
8
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361005, China.
9
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361005, China Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 cxiao@scripps.edu whliu@xmu.edu.cn guofu@xmu.edu.cn.

Abstract

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-κB 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.

PMID:
27481129
PMCID:
PMC4995083
DOI:
10.1084/jem.20160204
[Indexed for MEDLINE]
Free PMC Article

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