Skin barrier immunity and ageing

Abstract

The skin is the outermost layer of the body with an extensive surface area of approximately 1·8 m² , and is the first line of defence against a multitude of external pathogens and environmental insults. The skin also has important homeostatic functions such as reducing water loss and contributing to thermoregulation of the body. The structure of the skin and its cellular composition work in harmony to prevent infections and to deal with physical and chemical challenges from the outside world. In this review, we discuss how the structural cells such as keratinocytes, fibroblasts and adipocytes contribute to barrier immunity. We also discuss specialized immune cells that are resident in steady-state skin including mononuclear phagocytes, such as Langerhans cells, dermal macrophages and dermal dendritic cells in addition to the resident memory T cells. Ageing results in an increased incidence of cancer and skin infections. As we age, the skin structure changes with thinning of the epidermis and dermis, increased water loss, and fragmentation of collagen and elastin. In addition, the skin immune composition is altered with reduced Langerhans cells, decreased antigen-specific immunity and increased regulatory populations such as Foxp3⁺ regulatory T cells. Together, these alterations result in decreased barrier immunity in the elderly, explaining in part their increased susceptiblity to cancer and infections.

Keywords: ageing; immunosenescence; skin; tissue resident.

Figure 1

Diagrammatic representation of human skin barrier immunity. The surface of the skin is covered in antimicrobial peptides and lipids, some of which originate from the sebaceous gland located near the hair follicle. The epidermis consists of keratinocytes forming stratified corneum, with melanocytes interspersed. Langerhans cells and T resident memory cells (T_rm) can also be found in the epidermis. The dermis has a more diverse collection of cells including structural cells such as fibroblasts, and immune cells such as dermal dendritic cells (DCs) and macrophages, CD4⁺ and CD8⁺ T_rm, mast cells and Foxp3⁺ T regulatory cells (Tregs), which are often located near the hair follicle. The final layer of the skin is the subcutaneous fat, which is primarily composed of adipocytes.

Figure 2

Structural changes in human skin with age. Young skin structure (left) and compared with older skin structure (right). Older skin has fragmented elastin and collagen, increasing water loss, which leads to skin dryness and increased wrinkles. In addition, the skin is thinner with all three layers being less thick then the younger counterpart.

Figure 3

Skin barrier immunity changes with age. Schematic showing the effect of age on skin‐resident populations. Negative/inhibitory effects are shown in red and positive/enhancing effects are shown in green. ECM, extracellular matrix; LC, Langerhans cell; MMP, matrix metalloproteinases; Treg, T regulatory cells.