Interleukin-33 Promotes REG3γ Expression in Intestinal Epithelial Cells and Regulates Gut MicrobiotaSummary

Yi Xiao; Xiangsheng Huang; Ye Zhao; Feidi Chen; Mingming Sun; Wenjing Yang; Liang Chen; Suxia Yao; Alex Peniche; Sara M. Dann; Jiaren Sun; George Golovko; Yuriy Fofanov; Yinglei Miao; Zhanju Liu; Daiwen Chen; Yingzi Cong

Cellular and Molecular Gastroenterology and Hepatology (Jan 2019)

Interleukin-33 Promotes REG3γ Expression in Intestinal Epithelial Cells and Regulates Gut MicrobiotaSummary

Yi Xiao,
Xiangsheng Huang,
Ye Zhao,
Feidi Chen,
Mingming Sun,
Wenjing Yang,
Liang Chen,
Suxia Yao,
Alex Peniche,
Sara M. Dann,
Jiaren Sun,
George Golovko,
Yuriy Fofanov,
Yinglei Miao,
Zhanju Liu,
Daiwen Chen,
Yingzi Cong

Affiliations

Yi Xiao: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, Sichuan, China
Xiangsheng Huang: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
Ye Zhao: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
Feidi Chen: Department of Pathology, University of Texas Medical Branch, Galveston, Texas
Mingming Sun: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
Wenjing Yang: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
Liang Chen: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
Suxia Yao: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
Alex Peniche: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
Sara M. Dann: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
Jiaren Sun: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
George Golovko: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas
Yuriy Fofanov: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas
Yinglei Miao: Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
Zhanju Liu: Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
Daiwen Chen: Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, Sichuan, China; Daiwen Chen, PhD, Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, Sichuan, China, 625014. fax: 86-28-82652669.
Yingzi Cong: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Department of Pathology, University of Texas Medical Branch, Galveston, Texas; Correspondence Address correspondence to: Yingzi Cong, PhD, Department of Microbiology and Immunology, University of Texas Medical Branch, 4.142C Medical Research Building, 301 University Boulevard, Galveston, Texas 77555-1019. fax: (409) 772-5065.

Journal volume & issue: Vol. 8, no. 1
pp. 21 – 36

Abstract

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Background & Aims: Regenerating islet-derived protein (REG3γ), an antimicrobial peptide, typically expressed by intestinal epithelial cells (IEC), plays crucial roles in intestinal homeostasis and controlling gut microbiota. However, the mechanisms that regulate IEC expression of REG3γ are still largely unclear. In this study, we investigated whether and how interleukin (IL) 33, an alarmin produced by IEC in response to injury, regulates REG3γ expression in IEC, thus contributing to intestinal homeostasis. Methods: IEC were isolated from wild-type and IL33-/- mice to determine expression of REG3γ and other antimicrobial peptides by quantitative real-time polymerase chain reaction and Western blot. IEC cell lines were used for mechanistic studies. 16S rRNA pyrosequencing analysis was used for measuring gut microbiota. Citrobacter rodentium was used for enteric infections. Results: The expression of REG3γ, but not β-defensins, in IECs of IL33-/- mice was significantly lower than wild-type mice. IL33 treatment induced IEC expression of REG3γ in both mice and human cell lines. Mechanistically, IL33 activated STAT3, mTOR, and ERK1/2 in IEC. Inhibition of these pathways abrogated IL33-induction of REG3γ. IL33-/- mice demonstrated higher bacteria loads and altered microbiota composition. IL33 did not directly inhibit bacterial growth, but promoted wild-type, not REG3γKO, IECs to kill bacteria in vitro. Consistently, C rodentium infection induced IEC IL33 expression, and IL33-/- mice demonstrated an impaired bacterial clearance with C rodentium infection. Conclusions: Our study demonstrated that IL33, which is produced by IEC in response to injury and inflammatory stimulation, in turn promotes IEC expression of REG3γ, and controls the gut microbiota of the host. Keywords: IEC, IL33, REG3γ, Microbiota

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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