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

Year: 2016

Type: article

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.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20160204

Authors: Wen-Hsien Liu, Seung Goo Kang, Zhe Huang, Cheng-Jang Wu, Hyun Yong Jin, Christian J. Maine, Yi Liu, Jovan Shepherd, Mohsen Sabouri-Ghomi, Alicia Gonzalez-Martin, Shunbin Xu, Alexander Hoffmann, Ye Zheng, Li-Fan Lu, Nengming Xiao, Guo Fu, Changchun Xiao

Institutions: Xiamen University, Scripps Research Institute, Kangwon National University, University of California San Diego, Moores Cancer Center, University of California, Los Angeles, Wayne State University, Kresge Eye Institute, Salk Institute for Biological Studies

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Pew Charitable Trusts, Cancer Research Institute, Lupus Research Institute, Lupus Research Alliance, National Research Foundation, National Natural Science Foundation of China, Kangwon National University, National Research Foundation of Korea, National Institutes of Health, Fundamental Research Funds for the Central Universities, National Eye Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases

OpenAlex ID: W2482433771