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Neutrophils Promote Amphiregulin Production in Intestinal Epithelial Cells through TGF-β and Contribute to Intestinal Homeostasis
- Source :
- The Journal of Immunology. 201:2492-2501
- Publication Year :
- 2018
- Publisher :
- The American Association of Immunologists, 2018.
-
Abstract
- Neutrophils are the first responders to sites of inflammation when the intestinal epithelial barrier is breached and the gut microbiota invade. Despite current efforts in understanding the role of neutrophils in intestinal homeostasis, the complex interactions between neutrophils and intestinal epithelial cells (IECs) is still not well characterized. In this study, we demonstrated that neutrophils enhanced production of amphiregulin (AREG), a member of the EGFR ligand family, by IECs, which promoted IEC barrier function and tissue repair. Depletion of neutrophils resulted in more severe colitis in mice because of decreased AREG production by IECs upon dextran sodium sulfate (DSS) insult. Administration of AREG restored epithelial barrier function and ameliorated colitis. Furthermore, neutrophil-derived TGF-β promoted AREG production by IECs. Mechanistically, TGF-β activated MEK1/2 signaling, and inhibition of MEK1/2 abrogated TGF-β–induced AREG production by IECs. Collectively, these findings reveal that neutrophils play an important role in the maintenance of IEC barrier function and homeostasis.
- Subjects :
- Male
0301 basic medicine
Neutrophils
Immunology
MAP Kinase Kinase 1
Inflammation
Gut flora
Amphiregulin
digestive system
Article
Mice
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
parasitic diseases
medicine
Animals
Homeostasis
Humans
Immunology and Allergy
Intestinal Mucosa
Colitis
Cells, Cultured
Barrier function
biology
Chemistry
Dextran Sulfate
Inflammatory Bowel Diseases
biology.organism_classification
medicine.disease
digestive system diseases
Cell biology
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
030220 oncology & carcinogenesis
Female
medicine.symptom
Signal transduction
tissues
Signal Transduction
Transforming growth factor
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 201
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....f2b0f7296420297a4df9bf66860fd73d