The immunological anatomy of the skin

The skin is the outermost organ of the body and is continuously exposed to external pathogens. Upon inflammation, various immune cells pass through, reside in or are recruited to the skin to orchestrate diverse cutaneous immune responses. To achieve this, immune cells interact with each other and even communicate with non-immune cells, including peripheral nerves and the microbiota. Immunologically important anatomical sites, such as skin appendages (for example, hair follicles and sweat glands) or postcapillary venules, act as special portal sites for immune cells and for establishing tertiary lymphoid structures, including inducible skin-associated lymphoid tissue. Here, we provide an overview of the key findings and concepts of cutaneous immunity in association with skin anatomy and discuss how cutaneous immune cells fine-tune physiological responses in the skin. This Review considers the unique anatomy of the cutaneous immune system. The authors explain how both protective and pathological immune responses are shaped in the skin, its associated appendages (such as hair follicles and sweat glands) and skin-associated lymphoid tissues.