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 Suda, Masahira Hattori and Hiroshi Kiyono ()
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Yosuke Kurashima: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Takaaki Kigoshi: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Sayuri Murasaki: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Fujimi Arai: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Kaoru Shimada: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Natsumi Seki: Keio University
Yun-Gi Kim: Keio University
Koji Hase: The University of Tokyo
Hiroshi Ohno: RIKEN Center for Integrative Medical Sciences
Kazuya Kawano: RIKEN Center for Integrative Medical Sciences
Hiroshi Ashida: Tokyo Medical and Dental University
Toshihiko Suzuki: Tokyo Medical and Dental University
Masako Morimoto: Chiba University
Yukari Saito: Chiba University
Ai Sasou: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Yuki Goda: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Yoshikazu Yuki: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo
Yutaka Inagaki: Tokai University
Hideki Iijima: Osaka University
Wataru Suda: RIKEN Center for Integrative Medical Sciences
Masahira Hattori: RIKEN Center for Integrative Medical Sciences
Hiroshi Kiyono: The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21277-2

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