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ResearchIn-Press PreviewGastroenterology Open Access | 10.1172/jci.insight.167910
1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2Laboratory for Immunological Memory, RIKEN IMS Center for Integrative Medical Science, Yokohama, Japan
3Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
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Published September 26, 2024 - More info
The pathogenesis of the murine model of autoimmune pancreatitis associated with IgG4-related disease (AIP/IgG4-RD) induced by administration of polyinosinic-polycytidylic acid, is incompletely understood. While it is known that murine and human AIP/IgG4-RD is driven by plasmacytoid dendritic cells (pDCs) producing IFN-α, the origin of these cells and their relation to effector T cells is not known. Here we show that murine AIP was initiated by TLR3-bearing conventional DCs in the uninflamed pancreas whose activation by TLR3 ligand (polyinosinic-polycytidylic acid) caused IFN-α, CXCL9, and CXCL10 secretion. This, in turn, induced pancreatic recruitment of CXCR3+ T cells and these T cells, via their secretion of CCL25, facilitated migration of pDCs bearing CCR9 into the pancreas. This established a feedback loop anchored by the now dominant pDC production of IFN-α and the continued CXCR3+ T cell facilitation of pDC migration. Remarkably, the interaction between CXCR3+ T cells and pDCs also existed at the functional levels since this interaction enhanced the production of CCL25 and IFN-α by CXCR3+ T cells and pDCs, respectively. Evidence presented here that a similar disease mechanism was present in human AIP/IgG4-RD creates new avenues of disease treatment.