Kinase signaling in the control of regulatory T cell function: molecular mechanisms and therapeutic implications

Regulatory T cells (Tregs) are central to immune regulation, preventing excessive immune responses, maintaining immune tolerance, and modulating inflammatory microenvironments. Dysregulation of Treg development, differentiation, proliferation, or function contributes significantly to autoimmune diseases, inflammatory disorders, and tumor immune evasion. Protein kinases, key mediators of cellular signaling, regulate diverse processes including motility, metabolism, transport, and cell cycle progression; their emerging roles in immune regulation make them promising therapeutic targets for inflammatory diseases, autoimmunity, and immunotherapy-treated cancers. Notably, protein kinases modulate Treg differentiation and function by controlling the expression of the lineage markers Forkhead box protein 3 (Foxp3, intracellular) and CD25 (cell surface). This mechanistic review addresses: (1) fundamental Treg characteristics, functions, and disease relevance; (2) protein kinase-mediated regulatory mechanisms in Tregs; and (3) progress on protein kinase inhibitors for Treg-related diseases. The review aims to outline the kinase regulatory network governing Treg biology and guide future identification of kinase targets for treating autoimmune, inflammatory, and malignant diseases.