Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity

Simon H Jiang; Nan Shen; Carola G Vinuesa

doi:10.1016/j.coi.2015.09.003

Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity

Curr Opin Immunol. 2015 Dec:37:21-7. doi: 10.1016/j.coi.2015.09.003. Epub 2015 Sep 30.

Authors

Simon H Jiang¹, Nan Shen², Carola G Vinuesa³

Affiliations

¹ Department of Immunology and Infectious Disease, John Curtin School of Medical Research and Centre for Personalised Immunology, Australian National University, Canberra, Australia; Department of Renal Medicine, The Canberra Hospital, Canberra, Australia; China Australia Centre for Personalised Immunology, Shanghai Renji Hospital, China and Australian National University, Australia. Electronic address: simon.jiang@anu.edu.au.
² China Australia Centre for Personalised Immunology, Shanghai Renji Hospital, China and Australian National University, Australia; Joint Molecular Rheumatology Laboratory of the Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China.
³ Department of Immunology and Infectious Disease, John Curtin School of Medical Research and Centre for Personalised Immunology, Australian National University, Canberra, Australia; China Australia Centre for Personalised Immunology, Shanghai Renji Hospital, China and Australian National University, Australia. Electronic address: carola.vinuesa@anu.edu.au.

PMID: 26432764
DOI: 10.1016/j.coi.2015.09.003

Abstract

T follicular helper (Tfh) cells are crucial to induce protective extrafollicular and germinal center antibody responses against protein antigens. Over the last decade, control of Tfh cell numbers has emerged as an important regulatory checkpoint which, when perturbed, may lead to production of autoantibodies. Recent progress in understanding how Tfh cells are kept limiting has revealed an important role for posttranscriptional control of gene expression mediated by microRNAs such as miR-17 ∼ 92, miR-155 and miR-146a, and the RNA-binding proteins Roquin and Regnase. Additionally, T cell microRNAs dysregulated in patients with systemic lupus erythematosus have been shown to influence processes such as DNA hypomethylation, IL-2 and CCL5 secretion, and Treg function, which contribute to autoantibody formation and tissue damage.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Autoantibodies / metabolism
Chemokine CCL5 / genetics
Chemokine CCL5 / metabolism
DNA Methylation
Germinal Center / immunology*
Humans
Interleukin-2 / genetics
Interleukin-2 / metabolism
Lupus Erythematosus, Systemic / immunology*
MicroRNAs / genetics
MicroRNAs / metabolism
RNA Interference
RNA-Binding Proteins / metabolism
Ribonucleases / metabolism
T-Lymphocytes, Helper-Inducer / immunology*
Transcription Factors / metabolism
Ubiquitin-Protein Ligases / metabolism

Substances

Autoantibodies
Chemokine CCL5
Interleukin-2
MicroRNAs
RC3H1 protein, human
RNA-Binding Proteins
Transcription Factors
Ubiquitin-Protein Ligases
Ribonucleases
ZC3H12A protein, human