Related Experiment Video
Updated: Mar 17, 2026
Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells
Wen-Hsien Liu1, Seung Goo Kang2, Zhe Huang3
1State 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.
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.
Insights
MicroRNA 155 (miR-155) is crucial for T follicular helper (Tfh) cell generation and function. It regulates Tfh cell proliferation and CD40 ligand expression by controlling the Peli1-c-Rel pathway.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- MicroRNA (miRNA) deficiency impacts T follicular helper (Tfh) cell development.
- The specific roles of individual miRNAs in Tfh cell generation are not well understood.
Purpose of the Study:
- To identify key miRNAs regulating Tfh cell generation and function.
- To elucidate the molecular mechanisms underlying miRNA-mediated regulation of Tfh cells.
Main Methods:
- Deep sequencing analysis of miRNAs in Tfh cells.
- Analysis of mutant mice deficient in specific miRNAs.
- Assessment of Tfh cell proliferation and CD40 ligand expression.
- Investigation of the miR-155-Peli1-c-Rel signaling pathway.
Main Results:
- A five-miRNA signature in Tfh cells was identified.
- miR-155, but not miR-22 or miR-183/96/182, is essential for Tfh cell generation and function.
- miR-155 deficiency resulted in impaired late-stage Tfh cell proliferation and reduced CD40 ligand expression.
- miR-155 was found to repress Peli1, which targets c-Rel for degradation.
Conclusions:
- A novel regulatory pathway involving miR-155, Peli1, and c-Rel in Tfh cell development was identified.
- This pathway is critical for controlling Tfh cell proliferation and CD40 ligand expression.
- miR-155 plays an essential role in the generation and function of T follicular helper cells.
More Related Videos
07:39Isolation of CD4+ T-cells and Analysis of Circulating T-follicular Helper cTfh Cell Subsets from Peripheral Blood Using 6-color Flow Cytometry
Published on: January 7, 2019
05:03Author Spotlight: Elucidating the Pathways of TFH Cell Differentiation in Acute LCMV Challenges
Published on: April 26, 2024
Related Concept Videos
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...