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GEO help: Mouse over screen elements for information. |
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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
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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.
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Overall design |
Amphiregulin producing cells, eosinophils and lung treated with HDM are assessed by RNA-seq.
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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 |
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Submission date |
May 25, 2018 |
Last update date |
Sep 12, 2018 |
Contact name |
Yuki Morimoto |
Organization name |
Chiba University
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Department |
Graduate school of Medicine
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Lab |
Immunology
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Street address |
1-8-1, Inohana, Chuoku
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City |
Chiba |
State/province |
Chiba |
ZIP/Postal code |
260-0856 |
Country |
Japan |
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Platforms (1) |
GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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Samples (18)
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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 |
GSM3154835 |
4_ST2High_IL33_IL2: ST2 high memory Th2 cells cultured with IL-2 + IL-33 for 3 days |
GSM3154836 |
5_ST2high_IL2: ST2 high memory Th2 cells cultured with IL-2 for 3 days |
GSM3154837 |
6_ST2high_IL33_IL2: ST2 high memory Th2 cells cultured with IL-2 + IL-33 for 3 days |
GSM3154838 |
2_C: Eosinophils cultured without Amphiregulin for 3 days |
GSM3154839 |
3_C: Eosinophils cultured without Amphiregulin for 3 days |
GSM3154840 |
4_C: Eosinophils cultured without Amphiregulin for 3 days |
GSM3154841 |
2_A: Eosinophils cultured with Amphiregulin for 3 days |
GSM3154842 |
3_A: Eosinophils cultured with Amphiregulin for 3 days |
GSM3154843 |
4_A: Eosinophils cultured with Amphiregulin for 3 days |
GSM3154844 |
Balbc_1: W.T. mouse lung treated with OVA |
GSM3154845 |
Balbc_2: W.T. mouse lung treated with OVA |
GSM3154846 |
Balbc_3: W.T. mouse lung treated with OVA |
GSM3154847 |
dGATA_1: K.O. mouse lung treated with OVA |
GSM3154848 |
dGATA_2: K.O. mouse lung treated with OVA |
GSM3154849 |
dGATA_3: K.O. mouse lung treated with OVA |
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Relations |
BioProject |
PRJNA473135 |
SRA |
SRP148972 |
Supplementary file |
Size |
Download |
File type/resource |
GSE114921_RAW.tar |
11.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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