NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE114921 Query DataSets for GSE114921
Status Public on Aug 21, 2018
Title Amphiregulin-producing pathogenic memory T helper-2 cells instruct eosinophils to secrete Osteopontin and facilitate airway fibrosis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Contributor(s) Morimoto Y, Hirahara K, Kiuchi M, Wada T, Ichikawa T, Kanno T, Okano M, Kokubo K, Onodera A, Sakurai D, Okamoto Y, Nakayama T
Citation(s) 29958800
Submission date May 25, 2018
Last update date Sep 12, 2018
Contact name Yuki Morimoto
Organization name Chiba University
Department Graduate school of Medicine
Lab Immunology
Street address 1-8-1, Inohana, Chuoku
City Chiba
State/province Chiba
ZIP/Postal code 260-0856
Country Japan
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (18)
GSM3154832 1_ST2High_IL2: ST2 high memory Th2 cells cultured with IL-2 for 3 days
GSM3154833 2_ST2High_IL33_IL2: ST2 high memory Th2 cells cultured with IL-2 + IL-33 for 3 days
GSM3154834 3_ST2High_IL2: ST2 high memory Th2 cells cultured with IL-2 for 3 days
Relations
BioProject PRJNA473135
SRA SRP148972

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE114921_RAW.tar 11.2 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap