Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has g...

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Main Authors: Kosuke Minaga, Tomohiro Watanabe, Akane Hara, Tomoe Yoshikawa, Ken Kamata, Masatoshi Kudo
Format: Article
Language:English
Published: Gastroenterology Council for Gut and Liver 2025-03-01
Series:Gut and Liver
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Online Access:http://gutnliver.org/journal/view.html?doi=10.5009/gnl240380
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author Kosuke Minaga
Tomohiro Watanabe
Akane Hara
Tomoe Yoshikawa
Ken Kamata
Masatoshi Kudo
author_facet Kosuke Minaga
Tomohiro Watanabe
Akane Hara
Tomoe Yoshikawa
Ken Kamata
Masatoshi Kudo
author_sort Kosuke Minaga
collection DOAJ
description Autoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has garnered great attention from clinicians, but its pathophysiology remains poorly understood. Recent discoveries indicate that plasmacytoid dendritic cell activation followed by robust production of type I interferon and interleukin-33 plays a key role in driving chronic fibro-inflammatory responses in both murine and human AIP. Furthermore, the compositional alterations in the gut microbiota, known as intestinal dysbiosis, triggered plasmacytoid dendritic cell-driven pathogenic type I interferon responses. Intestinal dysbiosis is associated with a breakdown in intestinal barrier function; thus, we examined whether the latter condition affects the development of experimental AIP. Our recent research has revealed that intestinal barrier disruption worsens experimental AIP by facilitating the translocation of pathogenic bacteria, such as Staphylococcus sciuri, to the pancreas from the gut. These results indicate the “gut-pancreas axis” underlies the immunopathogenesis of AIP, and the maintenance of intestinal barrier integrity can prevent the worsening of AIP by inhibiting pancreatic colonization by harmful gut bacteria. In this mini review, the interactions between AIP development and gut microbiota are discussed with the aim of providing useful information not only for researchers but also for clinicians.
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spelling doaj-art-8d110f301de54766ae463bedd4b2cfb12025-08-20T02:06:28ZengGastroenterology Council for Gut and LiverGut and Liver1976-22832025-03-0119217117610.5009/gnl240380gnl240380Gut Microbiota Involved in the Immunopathogenesis of Autoimmune PancreatitisKosuke Minaga0Tomohiro Watanabe1Akane Hara2Tomoe Yoshikawa3Ken Kamata4Masatoshi Kudo5Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanAutoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has garnered great attention from clinicians, but its pathophysiology remains poorly understood. Recent discoveries indicate that plasmacytoid dendritic cell activation followed by robust production of type I interferon and interleukin-33 plays a key role in driving chronic fibro-inflammatory responses in both murine and human AIP. Furthermore, the compositional alterations in the gut microbiota, known as intestinal dysbiosis, triggered plasmacytoid dendritic cell-driven pathogenic type I interferon responses. Intestinal dysbiosis is associated with a breakdown in intestinal barrier function; thus, we examined whether the latter condition affects the development of experimental AIP. Our recent research has revealed that intestinal barrier disruption worsens experimental AIP by facilitating the translocation of pathogenic bacteria, such as Staphylococcus sciuri, to the pancreas from the gut. These results indicate the “gut-pancreas axis” underlies the immunopathogenesis of AIP, and the maintenance of intestinal barrier integrity can prevent the worsening of AIP by inhibiting pancreatic colonization by harmful gut bacteria. In this mini review, the interactions between AIP development and gut microbiota are discussed with the aim of providing useful information not only for researchers but also for clinicians.http://gutnliver.org/journal/view.html?doi=10.5009/gnl240380autoimmune pancreatitisimmunoglobulin g4-related diseaseinnate immunitygastrointestinal microbiotadysbiosis
spellingShingle Kosuke Minaga
Tomohiro Watanabe
Akane Hara
Tomoe Yoshikawa
Ken Kamata
Masatoshi Kudo
Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
Gut and Liver
autoimmune pancreatitis
immunoglobulin g4-related disease
innate immunity
gastrointestinal microbiota
dysbiosis
title Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
title_full Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
title_fullStr Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
title_full_unstemmed Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
title_short Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
title_sort gut microbiota involved in the immunopathogenesis of autoimmune pancreatitis
topic autoimmune pancreatitis
immunoglobulin g4-related disease
innate immunity
gastrointestinal microbiota
dysbiosis
url http://gutnliver.org/journal/view.html?doi=10.5009/gnl240380
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