GSE114921
Amphiregulin-producing pathogenic memory T helper-2 cells instruct eosinophils to secrete Osteopontin and facilitate airway fibrosis
Memory helper T cells provide long-lasting host defeMemory helper T cells provide long-lasting host defense against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma.  Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes.  The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown.  We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2hi memory T helper-2 (Th2) cells.  Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein.  IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis.  The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils.  Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma.  Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes.  The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown.  We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2 hi memory T helper-2 (Th2) cells.  Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein.  IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis.  The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils.  Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. Overall design: Amphiregulin producing cells, eosinophils and lung treated with HDM are assessed by RNA-seq.