Mechanisms regulating skin immunity and inflammation

Key Points Monocytes and macrophages are increasingly recognized as important effector cells in inflammatory skin reactions. Depending on the cytokine milieu, they can either promote or attenuate the inflammatory response. In addition, they function in immune surveillance, thereby supporting the early detection of environmental threats. An increased understanding of different dendritic cell subsets in the skin, their developmental origin and dependence on different transcription factors and their contribution to various effector states of skin immunity opens new avenues for immune modulation. Recent studies have highlighted the importance of tissue-resident memory lymphocytes in establishing both effector and regulatory immune memory at skin tissue sites and the role of these cells in providing protection from pathogens. Epidermal keratinocytes have important immunoregulatory functions and contribute to the maintenance of immune homeostasis and the regulation of immune and inflammatory responses in the skin. Studies in mouse models suggest that keratinocyte-intrinsic mechanisms can contribute to the initiation of skin inflammation. Microorganisms that colonize the surface of the skin interact with epithelial and immune cells and have important functions in regulating immune homeostasis and inflammation in the skin. Immune homeostasis in the skin requires dynamic crosstalk between epithelial, stromal and immune cells, which is influenced by environmental insults and commensal microorganisms. Here, the authors highlight recent studies that provide an insight into the immunoregulatory mechanisms that mediate host defence and prevent chronic inflammation in the skin. Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.