ILCs in gut, lung, and skin. (A) In the healthy situation, ILC3s produce IL-22 to maintain the epithelial barrier, generate antimicrobial products (such as RegIIIβ, RegIIIγ, and β-defensins), and suppress the reactivity of commensal bacteria-specific T cells (left panel). Crohn disease is characterized by an accumulation of IFN-γ–producing ILC1s (middle panel). During intestinal inflammation, ILC3s produce IL-22 to maintain epithelial barrier homeostasis. CRC develops when this autoregenerative function is not switched off in time (right panel). (B) Airway hypersensitivity is characterized by stromal production of TSLP and IL-33 that induces IL-5 and IL-13 production by ILC2s and subsequent recruitment and activation of eosinophils and mast cells (left panel). Upon viral airway infection, however, ILC2s are induced to produce amphiregulin, which is involved in airway epithelium repair and maintenance, and thereby function as tissue-protective cells (right panel). (C) In the healthy skin, ILC2s maintain close interactions with mast cells, suppressing their proinflammatory function, whereas ILC3s are involved in wound repair (left panel). Atopic dermatitis is an ILC2-mediated disease (middle panel), whereas ILC3s are accumulated in psoriasis (right panel).