Fig. 2

The role of the ILC family in lung homeostasis, cell-cell interactions and tissue repair. a In response to infection or allergen exposure, epithelial cell- and myeloid cell-derived IL-25, IL-33 and TSLP elicit ILC2s responses in the lung. ILC2 responses can be enhanced by basophil-derived IL-4 or mast cell-derived PGD2. Activated ILC2s can subsequently promote IL-5-mediated eosinophil recruitment, IL-13-mediated AMac differentiation, or MHCII-mediated enhancement of Th2 cell responses, resulting in allergy and fibrosis. However, ILC1-derived IL-27 and IFN-γ can antagonize the function of ILC2s and type 2 innate immune responses. Furthermore, ILC2s proliferate in response to lymphoid-derived IL-2 and produce large amounts of Th2 cytokines, including IL-5, IL-6 and IL-13. IL-5 and IL-6 regulate B cell antibody production and the self-renewal of B1 cells. b After infection in the lung, airway epithelial cells are damaged and produce IL-33. ILC2s respond to IL-33 and produce amphiregulin, which promotes the repair of the airway epithelium. Together with autocrine IL-9 production, the IL-33 produced by macrophages, DCs, mast cells, NKTs and lymphoid cells enhances the repair function of ILCs. c In the innate inflammatory response in the lung, alveolar type II cells produce IL-33 and TSLP, which synergistically induce ILC2s to produce IL-5 and IL-13. IL-5 and IL-13 are known to promote mucus production