Regulatory T cells in skin regeneration and wound healing

Abstract

As the body’s integumentary system, the skin is vulnerable to injuries. The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality. To this end, multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue. Such temporally- and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation. In this context, regulatory T cells (Tregs) hold a key role in balancing immune homeostasis and mediating cutaneous wound healing. A comprehensive understanding of Tregs’ multifaceted field of activity may help decipher wound pathologies and, ultimately, establish new treatment modalities. Herein, we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair. Further, we discuss how Tregs operate during fibrosis, keloidosis, and scarring.

Cutaneous‐immuno‐neuro‐endocrine (CINE) system: A complex enterprise transforming skin into a super organ

“…Apart from the native skin cells mentioned above, the skin harbours a variety of important cutaneous immune cells (CICs): antigen presenting cell (APCs) like Langerhans cells (LCs) and memory CD8 + T cells are located in the epidermis while macrophages, innate lymphoid cells, natural killer cells, mast cells, dermal dendritic cells (dDCs), T cells including T‐regulatory cells (T regs), natural killer (NK) cells and B cells constitute CICs population in the dermis (Figure 1). 35–37 The cutaneous immune arm mediates an interplay of various immune mechanisms employing the innate and adaptive components providing for an effective cutaneous immunosurveillance 38,39 . For instance, the resident APCs in the skin along with other innate CICs such as mast cells secrete many cytokines and chemokines.…”

Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?

“…However, although pre-clinical studies are enlightening, significantly more basic science research regarding the precise role of T-regs in wound healing and the mechanism by which they mediate it is required. Knoedler et al [ 43 ] discussed future directions of T-regs, noting that chimeric antigen receptor-equipped T-regs may deliver promising treatment options for wound healing due to chimeric antigen receptor-T-regs proven track record in controlling alloimmune-mediated rejection in human skin grafts. However, potential side-effects such as T-reg overstimulation or exhaustion have to be further investigated pre-clinical prior to clinical application.…”

The impact of glucocorticoids therapy on cutaneous wounds in Kawasaki disease: A meta‐analysis of randomized controlled trials

“…The integumentary system serves as a critical interface between the external environment and internal physiological processes, with skin involvement being a hallmark of KD. 14 The characteristic polymorphous exanthem, which includes erythematous rash, desquamation and indurated edema, represents a distinctive feature of the disease. 9 The dynamic interplay between the systemic inflammatory response and the cutaneous manifestations in KD necessitates a nuanced evaluation of therapeutic interventions, particularly glucocorticoid therapy, to ascertain its impact on skin wounds.…”

“…The integumentary system serves as a critical interface between the external environment and internal physiological processes, with skin involvement being a hallmark of KD 14 . The characteristic polymorphous exanthem, which includes erythematous rash, desquamation and indurated edema, represents a distinctive feature of the disease 9 .…”