GSE114921 Amphiregulin-producing pathogenic memory T helper-2 cells instruct eosinophils to secrete Osteopontin and facilitate airway fibrosis

Contributors : Yuki Morimoto ; Kiyoshi Hirahara ; Masahiro Kiuchi ; Tomoko Wada ; Tomomi Ichikawa ; Toshio Kanno ; Mikiko Okano ; Kota Kokubo ; Atsushi Onodera ; Daijyu Sakurai ; Yoshitaka Okamoto ; Toshinori NakayamaSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMemory 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 d...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research