Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation

Yosuke Kurashima, Takaaki Kigoshi, Sayuri Murasaki, Fujimi Arai, Kaoru Shimada, Natsumi Seki, Yun Gi Kim, Koji Hase, Hiroshi Ohno, Kazuya Kawano, Hiroshi Ashida, Toshihiko Suzuki, Masako Morimoto, Yukari Saito, Ai Sasou, Yuki Goda, Yoshikazu Yuki, Yutaka Inagaki, Hideki Iijima, Wataru SudaMasahira Hattori, Hiroshi Kiyono

Research output: Contribution to journalArticlepeer-review

Abstract

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF–dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn’s diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas–intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.

Original languageEnglish
Article number1067
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - 2021 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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