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 Dann-Grice, Zhanju Liu, Yingzi Cong

Research output: Contribution to journalArticle

3 Citations (Scopus)

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

Fingerprint

Neutrophils
Homeostasis
Epithelial Cells
Colitis
Dextran Sulfate
Amphiregulin
Maintenance
Ligands
Inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Neutrophils promote amphiregulin production in intestinal epithelial cells through TGF-β and contribute to intestinal homeostasis. / Chen, Feidi; Yang, Wenjing; Huang, Xiangsheng; Cao, Anthony T.; Bilotta, Anthony J.; Xiao, Yi; Sun, Mingming; Chen, Liang; Ma, Chunyan; Liu, Xiuping; Liu, Chang Gong; Yao, Suxia; Dann-Grice, Sara; Liu, Zhanju; Cong, Yingzi.

In: Journal of Immunology, Vol. 201, No. 8, 15.10.2018, p. 2492-2501.

Research output: Contribution to journalArticle

Chen, F, Yang, W, Huang, X, Cao, AT, Bilotta, AJ, Xiao, Y, Sun, M, Chen, L, Ma, C, Liu, X, Liu, CG, Yao, S, Dann-Grice, S, Liu, Z & Cong, Y 2018, 'Neutrophils promote amphiregulin production in intestinal epithelial cells through TGF-β and contribute to intestinal homeostasis', Journal of Immunology, vol. 201, no. 8, pp. 2492-2501. https://doi.org/10.4049/jimmunol.1800003
Chen, Feidi ; Yang, Wenjing ; Huang, Xiangsheng ; Cao, Anthony T. ; Bilotta, Anthony J. ; Xiao, Yi ; Sun, Mingming ; Chen, Liang ; Ma, Chunyan ; Liu, Xiuping ; Liu, Chang Gong ; Yao, Suxia ; Dann-Grice, Sara ; Liu, Zhanju ; Cong, Yingzi. / Neutrophils promote amphiregulin production in intestinal epithelial cells through TGF-β and contribute to intestinal homeostasis. In: Journal of Immunology. 2018 ; Vol. 201, No. 8. pp. 2492-2501.
@article{f4c2009624da4ff3a9b35689996bc715,
title = "Neutrophils promote amphiregulin production in intestinal epithelial cells through TGF-β and contribute to intestinal homeostasis",
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.",
author = "Feidi Chen and Wenjing Yang and Xiangsheng Huang and Cao, {Anthony T.} and Bilotta, {Anthony J.} and Yi Xiao and Mingming Sun and Liang Chen and Chunyan Ma and Xiuping Liu and Liu, {Chang Gong} and Suxia Yao and Sara Dann-Grice and Zhanju Liu and Yingzi Cong",
year = "2018",
month = "10",
day = "15",
doi = "10.4049/jimmunol.1800003",
language = "English (US)",
volume = "201",
pages = "2492--2501",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Neutrophils promote amphiregulin production in intestinal epithelial cells through TGF-β and contribute to intestinal homeostasis

AU - Chen, Feidi

AU - Yang, Wenjing

AU - Huang, Xiangsheng

AU - Cao, Anthony T.

AU - Bilotta, Anthony J.

AU - Xiao, Yi

AU - Sun, Mingming

AU - Chen, Liang

AU - Ma, Chunyan

AU - Liu, Xiuping

AU - Liu, Chang Gong

AU - Yao, Suxia

AU - Dann-Grice, Sara

AU - Liu, Zhanju

AU - Cong, Yingzi

PY - 2018/10/15

Y1 - 2018/10/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85054771770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054771770&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1800003

DO - 10.4049/jimmunol.1800003

M3 - Article

C2 - 30171165

AN - SCOPUS:85054771770

VL - 201

SP - 2492

EP - 2501

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -