| Project/Area Number |
17K09468
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内田 一茂 関西医科大学, 医学部, 准教授 (40411516)
西尾 彰功 関西医科大学, 医学部, 准教授 (50362463)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | IgG4関連疾患 / 自己免疫性膵炎 / 自然免疫 / IgG4関連硬化性胆管炎 / 消化器内科学 / 膵臓学 / 胆道学 |
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| Outline of Final Research Achievements |
Recently, abnormal innate immunity has been demonstrated in some patients with IgG4-RD. Activation of NOD-2 and toll-like receptor (TLR) ligands on monocytes or basophils from patients with IgG4-related AIP enhances IgG4 responses via B-cell activating factor (BAFF) and IL-13, although the specific pathogens still remain unclear 47,48). We identified abundant infiltration of TLR-7 positive M2-macrophages in the pancreatic tissues from type 1 AIP, and activated basophils via TLR signaling in the peripheral blood were increased and infiltrated into the pancreatic tissue, which suggested that increased activated basophils may be involved in the development of type 1 AIP. We identified increased miRNA-21-5p from circulating extracellular vesicles and IL-35 was significantly increased in type 1 AIP. In animal models, mice activated by ligands of TLR3 or TLR4, and TNP-IgE mutant mice induce immune-mediated cholangitis, pancreatitis, and sialadenitis similar to human IgG4-RD.
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| Academic Significance and Societal Importance of the Research Achievements |
自己免疫性膵炎はIgG4関連疾患の膵病変であり、現在指定難病となっているが、原因不明で治療法も確立していない。本研究により、自然免疫系異常が疾患の病態や発症に関連することが示唆された。特に、IL-35、好塩基球、miRNA-21などが標的分子や細胞として新規治療ターゲットになる可能性があり、その意義は高いと思われる。
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