Neutrophils Promote Amphiregulin Production in Intestinal Epithelial Cells through TGF-β and Contribute to Intestinal Homeostasis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Feidi ChenYingzi Cong

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.

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Citations

Jul 22, 2020·Journal of Clinical Laboratory Analysis·Feng ZhangPhilipp-Alexander Neumann
Dec 11, 2019·International Journal of Molecular Sciences·Xiang Xue, Daniel M Falcon
Jul 23, 2019·The Journal of Clinical Investigation·Jennifer C BrazilCharles A Parkos
Sep 22, 2020·Journal of Photochemistry and Photobiology. B, Biology·Marina de Paula-SilvaAdriana Lino-Dos-Santos-Franco
Nov 17, 2020·Frontiers in Medicine·Mahmood Yaseen HachimRifat Hamoudi
Feb 25, 2021·Cell & Bioscience·Mary Yinghua ZhangJingwu Xie
Mar 17, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Na ZhaoTao Wang
Apr 17, 2021·Science·Elisabeth E L NyströmMalin E V Johansson
May 1, 2021·International Journal of Molecular Sciences·Kamil Karolczak, Cezary Watala
Jul 3, 2021·Cancers·Ester Gonzalez-SanchezIsabel Fabregat

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