Figure 2Airway Inflammation, Smooth Muscle Constriction, and Airway Remodeling Generated by Innate Effectors
(Left) PAMPs associated with microbes or allergens such as peptidoglycan, zymosan, chitin, and mannose-rich ligands from dust mites and fungi, directly elicit arachidonic acid metabolism and inflammatory cytokines from tissue-resident effector cells such as DCs, MCs, and macrophages (MΦ). Chitin-induced eosinophilic inflammation is independent of STAT6 and RAG2. (Center) Allergens stimulate epithelial cell generation of IL-33, TSLP, and IL-25. While TSLP induces MC generation of Th2 cytokines, IL-33 acts more broadly on MCs, eosinophils (Eo), and basophils (B) to elicit Th2 cytokines. IL-33-induced goblet cell metaplasia and AHR is independent of RAG2. IL-25 induces IL-4, IL-5, and IL-13 production from a NBNT cell population, and stimulates i NKTs to generate IL-13 and promote AHR and airway remodeling. IL-25 can induce AHR in Il4−/−Il5−/−Il9−/−Il13−/− mice. (Right) dsDNA or viral infection induces epithelial cells to produce TSLP which activates MCs to generate Th2 cytokines. i NKTs, activated by viral infection, generate IL-13 and activate IL-13-producing macrophages, in the absence of CD4+ cells, to promote AHR and remodeling.