Innate Lymphocytes in Psoriasis

Skin is a fundamental component of our host defense system that provides a dynamic physical and chemical barrier against pathogen invasion and environmental insults. Cutaneous barrier function is mediated by complex interactions between structural cells such as keratinocytes and diverse lineages of immune cells. In contrast to the protective role of these intercellular interactions, uncontrolled immune activation can lead to keratinocyte dysfunction and psoriasis, a chronic inflammatory disease affecting 2% of the global population. Despite some differences between human and murine skin, animal models of psoriasiform inflammation have greatly informed clinical approaches to disease. These studies have helped to identify the interleukin (IL)-23-IL-17 axis as a central cytokine network that drives disease. In addition, they have led to the recent description of long-lived, skin-resident innate lymphocyte and lymphoid cells that accumulate in psoriatic lesions. Although not completely defined, these populations have both overlapping and unique functions compared to antigen-restricted alpha beta T lymphocytes, the latter of which are well-known to contribute to disease pathogenesis. In this review, we describe the diversity of innate lymphocytes and lymphoid cells found in mammalian skin with a special focus on alpha beta T cells, Natural Killer T cells and Innate Lymphoid cells. In addition, we discuss the effector functions of these unique leukocyte subsets and how each may contribute to different stages of psoriasis. A more complete understanding of these cell types that bridge the innate and adaptive immune system will hopefully lead to more targeted therapies that mitigate or prevent disease progression.