Nucleotide-binding oligomerization domain 1 acts in concert with the cholecystokinin receptor agonist, cerulein, to induce IL-33-dependent chronic pancreatitis

Mucosal Immunology
Tomohiro WatanabeWarren Strober

Abstract

Nucleotide-binding oligomerization domain 1 (NOD1) fulfills important host-defense functions via its responses to a variety of gut pathogens. Recently, however, we showed that in acute pancreatitis caused by administration of cholecystokinin receptor (CCKR) agonist (cerulein) NOD1 also has a role in inflammation via its responses to gut commensal organisms. In the present study, we explored the long-term outcome of such NOD1 responsiveness in a new model of chronic pancreatitis induced by repeated administration of low doses of cerulein in combination with NOD1 ligand. We found that the development of chronic pancreatitis in this model requires intact NOD1 and type I IFN signaling and that such signaling mediates a macrophage-mediated inflammatory response that supports interleukin (IL)-33 production by acinar cells. The IL-33, in turn, has a necessary role in the induction of IL-13 and TGF-β1, factors causing the fibrotic reaction characteristic of chronic pancreatitis. Interestingly, the Th2 effects of IL-33 were attenuated by the concomitant type I IFN response since the inflammation was marked by clear increases in IFN-γ and TNF-α production but only marginal increases in IL-4 production. These studies establish chronic pan...Continue Reading

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Citations

Apr 5, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomohiro WatanabeMasatoshi Kudo
May 28, 2019·International Immunology·Tomohiro WatanabeWarren Strober
Jan 5, 2020·Clinical Journal of Gastroenterology·Sho MasakiMasatoshi Kudo
Nov 17, 2016·Mucosal Immunology·T WatanabeW Strober
Oct 13, 2017·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Tomohiro WatanabeWarren Strober
May 2, 2018·World Journal of Gastroenterology : WJG·Kosuke MinagaMasatoshi Kudo
Sep 11, 2020·International Immunology·Hajime HonjoMasatoshi Kudo
Jan 26, 2021·Digestive Diseases and Sciences·Kosuke MinagaMasatoshi Kudo
Apr 10, 2021·Frontiers in Immunology·Tomoe YoshikawaMasatoshi Kudo
May 28, 2021·World Journal of Gastroenterology : WJG·Akane HaraMasatoshi Kudo
Jun 30, 2021·Journal of Leukocyte Biology·Yuli LinXuguang Yang

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