Neutrophils promote amphiregulin production in intestinal epithelial cells through TGF-β and contribute to intestinal homeostasis

Feidi Chen, Wenjing Yang, Xiangsheng Huang, Anthony T. Cao, Anthony J. Bilotta, Yi Xiao, Mingming Sun, Liang Chen, Chunyan Ma, Xiuping Liu, Chang Gong Liu, Suxia Yao, Sara M. Dann, Zhanju Liu, Yingzi Cong

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2492-2501
Number of pages10
JournalJournal of Immunology
Volume201
Issue number8
DOIs
StatePublished - Oct 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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