Administration of indigo naturalis inhibits the development of autoimmune pancreatitis through IL-22-mediated signaling pathways

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16975
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kindai University
• Principal Investigator: Kamata Ken 近畿大学, 医学部, 医学部講師 (70548495)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 自己免疫性膵炎

Outline of Final Research Achievements

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in hematopoietic and non-hematopoietic cells. In this study, we tried to examine whether AhR activation suppresses development of experimental autoimmune pancreatitis (AIP) caused by activation of plasmacytoid dendritic cells (pDCs) producing IFN-α and IL-33. Experimental AIP was induced in MRL/MpJ mice by repeated injection of polyinosinic-polycytidylic acid (poly(I:C)). Activation of AhR by indole-3-pyruvic acid (IPA) and indigo naturalis (IN) in the diet inhibited development of experimental AIP, which effects were independent of activation of pDCs producing IFN-α and IL-33. Sensing of IPA and IN by AhRs led to a robust production of IL-22 by pancreatic islet α cells. Blockade of IL-22 signaling pathways completely canceled beneficial effect of AhR ligands on experimental AIP. Serum concentrations of IL-22 were elevated in patients with type 1 AIP after induction of remission by prednisolone.

Free Research Field

消化器病

Academic Significance and Societal Importance of the Research Achievements

「AhR-IL-22経路による膵臓腺房構造の恒常性の維持」は自己免疫性膵炎に対する抑制効果を持つことが明らかとなった。本研究の成果により、基礎的にはAhRの活性化が自己免疫性膵炎の発症に果たす役割を明らかにすることができた。また、臨床的には「青黛によるAhRの活性化」を用いた自己免疫性膵炎の新規治療法の開発につながる可能性が示唆された。このように、実験的自己免疫性膵炎における申請者自らの成果に基づいて計画された本研究により、自己免疫性膵炎の病態生理の解明とその臨床応用の双方につながるという点で学術的意義や社会的意義の高い研究成果を得ることができた。