Critical Role of RNA Binding Proteins in Regulatory T Cell Function and Immune Balance

Recent advances in immunology have highlighted the vital role of RNA binding proteins (RBPs) in maintaining immune homeostasis through their influence on regulatory T cells (Tregs). Researchers from the Babraham Institute have uncovered that specific members of the ZFP36 family of RBPs are crucial for the proper functioning of Tregs, which are essential for modulating immune responses and preventing excessive inflammation. These proteins regulate gene expression post-transcriptionally by binding to messenger RNA, affecting its stability, degradation, and translation.

In their study, the team used genetically modified mice lacking two key ZFP36 family members, Zfp36l1 and Zfp36l2, specifically in Treg cells. The absence of these RBPs led to significant immune dysregulation characterized by increased inflammation, elevated cytokine production, and heightened levels of circulating antibodies. Further sequencing analyses revealed that ZFP36 RBPs control numerous genes involved in pathways critical for immune regulation, including responses to cytokines such as IL-2 and IL-7, as well as the cytokine interferon-gamma (IFNg), which promotes inflammation.

The findings demonstrate that ZFP36 proteins enable Tregs to respond appropriately to molecular signals that regulate immune activity. Disruption in their function impairs the Tregs' capacity to maintain immune balance, highlighting their importance in preventing age-related chronic inflammation. This research advances our understanding of the molecular mechanisms behind immune regulation and suggests potential targets for therapeutic strategies aimed at controlling inflammation and related age-associated health conditions.

Published in Nature Communications, this study represents the first exploration of ZFP36 family proteins in Treg cell regulation, emphasizing their significance in immune homeostasis and the potential implications for treating chronic inflammatory diseases.