Regulation of CD8+ T Cell Biology by RNA-Binding Proteins: Molecular Mechanisms and Promising Therapeutic Innovations

Immune-related diseases such as infectious diseases, cancer, autoimmune diseases, neuroinflammatory diseases, immunodeficiencies, and immunopathologies during organ transplants continue to pose significant health challenges worldwide, contributing to substantial morbidity, mortality, and societal burden. CD8+ T cells are a specialized class of T lymphocytes that play a critical role in adaptive immunity by directly recognizing and eliminating virus-infected cells and malignant tumor cells. Effector CD8+ T cells play an important role in the acute immune response, whereas long-lived memory CD8+ T cells protect the body from previously encountered antigens. The biology of CD8+ T cells is governed by precise gene expression, and its dysregulation can lead to immunopathology. While epigenetic and transcriptional regulation of CD8+ T cells has been extensively studied, we are only beginning to understand the molecular factors and biological pathways involved in the post-transcriptional and translational regulation of CD8+ T cell biology. Furthermore, much remains to be studied about the regulation of recently discovered “poised” cytokine-encoding transcripts in resting memory CD8+ T cells. In this article, I discuss our current understanding of the role of RNA-binding proteins, particularly the ZFP36 family, in regulating the biology of CD8+ T cells. I also discuss the function of RNA-binding proteins in other immune cells, particularly in the context of dysregulated pro-inflammatory responses and cancer progression, emphasizing the need for further systematic investigations in CD8+ T cells. Finally, I discuss how modulating the activity of RNA-binding proteins in CD8+ T cells could drive therapeutic innovations for a broad range of immune-related diseases.