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

Feidi Chen | Zendy; Wenjing Yang | Zendy; Xiangsheng Huang | Zendy; Anthony Cao | Zendy; Anthony J. Bilotta | Zendy; Yi Xiao | Zendy; Mingming Sun | Zendy; Liang Chen | Zendy; Chunyan Ma | Zendy; Xiuping Liu | Zendy; ChangGong Liu | Zendy; Suxia Yao | Zendy; Sara M. Dann | Zendy; Zhanju Liu | Zendy; Yingzi Cong | Zendy

Open Access

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

Author(s) -

Feidi Chen,

Wenjing Yang,

Xiangsheng Huang,

Anthony Cao,

Anthony J. Bilotta,

Yi Xiao,

Mingming Sun,

Liang Chen,

Chunyan Ma,

Xiuping Liu,

ChangGong Liu,

Suxia Yao,

Sara M. Dann,

Zhanju Liu,

Yingzi Cong

Publication year - 2018

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1800003

Subject(s) - amphiregulin , homeostasis , barrier function , colitis , microbiology and biotechnology , chemistry , inflammation , intestinal epithelium , immunology , biology , epithelium , receptor , epidermal growth factor receptor , biochemistry , genetics

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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