Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity

• Posttranscriptional control of gene expression limits Tfh cells and autoimmunity.
• Roquin and Regnase induce decay of shared mRNA targets in distinct compartments.
• miR-17∼92 and miR-155 promote Tfh cell formation whereas miR-146a limits Tfh cells.
• T cell miRNAs dysregulated in SLE influence DNA methylation, IL-2 secretion and Tregs.

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.