RT Journal Article
SR Electronic
T1 A miR-155–Peli1–c-Rel pathway controls the generation and function of T follicular helper cells
JF The Journal of Experimental Medicine
JO J Exp Med
FD Rockefeller University Press
SP 1901
OP 1919
DO 10.1084/jem.20160204
VO 213
IS 9
A1 Liu, Wen-Hsien
A1 Kang, Seung Goo
A1 Huang, Zhe
A1 Wu, Cheng-Jang
A1 Jin, Hyun Yong
A1 Maine, Christian J.
A1 Liu, Yi
A1 Shepherd, Jovan
A1 Sabouri-Ghomi, Mohsen
A1 Gonzalez-Martin, Alicia
A1 Xu, Shunbin
A1 Hoffmann, Alexander
A1 Zheng, Ye
A1 Lu, Li-Fan
A1 Xiao, Nengming
A1 Fu, Guo
A1 Xiao, Changchun
YR 2016
UL http://jem.rupress.org/content/213/9/1901.abstract
AB 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.