The Dynamics of the Skin's Immune System

Abstract

The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host defense as well as tissue homeostasis. In the event of an insult, the skin-resident immune cells are crucial not only for prevention of infection but also for tissue reconstruction. Deregulation of immune responses often leads to impaired healing and poor tissue restoration and function. In this review, we will discuss the defensive components of the skin and focus on the function of skin-resident immune cells in homeostasis and their role in wound healing.

Keywords: impaired wound healing; inflammation; scarring; skin immune responses; skin resident immune cells; wound healing.

Figure 1

Schematic of normal and impaired wound healing. The inflammatory phase is hallmarked by infiltration of the wound by activated immune cells. Chemotaxis of immune cells to the injury site is facilitated by the presence of inflammatory mediators, which can be produced by skin-resident cells such as keratinocytes, dermal dendritic cells, Langerhans cells, and macrophages. The proliferative phase is characterized by expansion of keratinocytes and endothelial cells to restore the barrier function of the skin and vasculature of the tissue, respectively. Fibroblasts are major producers of collagen fibers in the wound bed and a source of de novo synthesized extracellular matrix. Efficient wound healing is characterized by the timely transition from the inflammatory to the proliferative phase. For this to occur, several events have to happen in concert: neutrophil numbers in the wound decrease, macrophages shift in phenotype from inflammatory to reparative, collagen deposition, and revascularization, thus facilitating wound closure. Chronic wounds are characterized by high levels of inflammation, and decreased production of growth factors, decreased proliferation of endothelial cells, and lack of re-epithelialization. For simplicity, the remodeling phase, certain immune cell types such as tissue-resident T lymphocytes, and nerve fibers are omitted. Wound complications such as bacterial infections and scarring are also omitted.