Type 2 immunity is a major driver of inflammatory allergic skin disease. However, the fundamental role of type 2 immunity in the context of skin homeostasis and its influence on skin tissue function is not well understood. Here we show that type 2 innate lymphoid cells (ILC2s) are the predominant skin tissue-resident immune cells that secrete type 2 cytokines in homeostasis. ILC2s in the skin have a distinct subset of activating signals when compared to tissue-resident ILC2s from other tissues. The activation of ILC2s and secretion of IL-13 is coupled to the stage of the hair follicle cycle. Deletion of ILC2s or the type 2 immunity signaling axis leads to increased proliferation of the hair follicle stem cells in a model of depilation-induced hair growth. Mice deficient in type 2 immunity leads to stem cell senescence. Deficiency of type 2 immunity leads to alteration of the skin-resident immune cell composition and tissue architecture. Our work identifies a previously uncharacterized function for type 2 immunity in homeostasis, and highlights the crosstalk between ILC2s and type 2 immunity in skin homeostasis.

Type 2 Immunity Influences Hair Follicle Stem Cell Proliferation and Skin Homeostasis