Immunomodulatory roles of regulatory T cells in cutaneous wound healing: mechanisms and therapeutic opportunities

Abstract

Cutaneous wound healing is a complex, tightly regulated biological process encompassing four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. While acute wounds typically progress through these stages in a coordinated manner, various pathological conditions, including diabetes mellitus and microbial infections, can impair this process, resulting in chronic, non-healing wounds. A sustained inflammatory phase characterizes chronic wounds and is commonly associated with systemic immune dysregulation. Emerging evidence show that regulatory T cells (Tregs) are critical modulators of tissue homeostasis and regeneration. Tregs exert their effects through the expression of immunoregulatory molecules and the secretion of anti-inflammatory cytokines, facilitating the resolution of inflammation, supporting angiogenesis, and promoting tissue repair. In the context of cutaneous wounds, skin-resident Tregs interact with both immune and non-immune cells, contributing to the restoration of barrier integrity. This review highlights the multifaceted roles of Tregs in cutaneous wound healing, with a particular emphasis on their contributions to the inflammatory and proliferative phases, including vascularization and regulation of fibroblasts. Furthermore, emerging therapeutic strategies targeting Tregs to modulate their function in chronic wound settings are discussed. These insights underscore the potential of Tregs as novel immunotherapeutic targets for enhancing wound repair and regeneration in chronic and diabetic wound pathologies.