The regenerative potential of skin and the immune system

Abstract

Skin has the natural ability to heal and replace dead cells regulated by a network of complex immune processes. This ability is conferred by the population of resident immune cells that act in coordination with other players to provide a homeostatic environment under constant challenge. Other than providing structure and integrity, the epidermis and dermis also house distinct immune properties. The dermal part is represented by fibroblasts and endothelial cells followed by an array of immune cells which includes dendritic cells (DCs), macrophages, mast cells, NK-cells, neutrophils, basophils, eosinophils, αβ T lymphocytes, B-cells and platelets. On the other hand, the functionally active immune cells in the epidermis comprise keratinocytes, DCs, NKT-cells, γδ T cells and αβ T cells (CD4+ and CD8+). Keratinocytes create a unique microenvironment for the cells of the immune system by promoting immune recognition and cellular differentiation. T lymphocytes exhibit tissue-specific tropism toward the epidermis and the lymphatic drainage system important for their function in immune regulation. This diversity in immune regulators makes the skin a unique organ to overcome pathogenic or foreign invasion. In addition, the highly coordinated molecular events make the skin an attractive model to understand and explore its regenerative potential.

Keywords: B cells; NK cells; basophils; dendritic cells; eosinophils; immune system of skin; macrophages; mast cells; neutrophils; skin regeneration; αβ T lymphocytes.

Figure 1

Different types of immune cells such as Langerhans cells, dendritic epidermal γδT cells (DETC), memory αβT cells (T_RM), dendritic cell macrophages, neutrophils, mast cells, T-regulatory cells (T-reg) and CD8⁺ T_EM Cells (Effector-Memory cells) are present in epidermis and dermis.

Figure 2

The microbial defense armor of fibroblasts. (A) Schematic representation of antimicrobial specificity for various Toll-like receptors (TLRs) expressed in the membrane and cytoplasmic organelles of fibroblasts. (B) Secretory factors responsible for elimination and prevention of microbial growth specifically in dermal and epidermal fibroblasts.

Figure 3

Schematic representation of various cytokines and chemokines secreted by keratinocytes in response to immune activation in skin injury. IFN represents Interferon and IL's represent Interleukin family of cytokines,  LL-37 is an important anti-microbial cathelicidin molecule whereas, CXCl, TGF-beta, TNF-alpha and beta-defensins are indicative of predominant chemoattractants.