(A) In response to various allergens and the influenza A virus subtype H3N1, lung epithelial cells produce IL-25 and IL-33 that promote IL-5 and IL-13 production from lung-resident group 2 ILCs that express the IL-33R (T1/ST2). IL-5 recruits eosinophils to the tissue, and IL-13 induces pathogenic epithelial cell proliferation and contraction of smooth muscle tissue, causing allergic airway inflammation and AHR. In the intestine, in a model of H. hepaticus-induced colitis, group 3 ILCs express the IL-23R and respond to IL-23 to produce IL-17A and IFN-γ that together contribute to colitis.
(B) In contrast, during infection with influenza virus A subtype H1N1, IL-33 derived from epithelial cells and macrophages promotes Areg expression from group 2 ILCs in the lung that express the IL-33R (T1/ST2), which support reparative epithelial cell proliferation. Additionally, in a model of OVA-induced AHR, lung resident RORγt+ group 3 ILCs produce IL-22 that limits the production of IL-5 and IL-13 that contributes to AHR.