Role of innate immunity in the development of autoimmune pancreatisitis
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 |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Kansai Medical University |
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 |
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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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD.2019
Author(s)
Nakamura T, Satoh-Nakamura T, Nakajima A, Kawanami T, Sakai T, Fujita Y, Iwao H, Miki M, Masaki Y, Okazaki T, Ishigaki Y, Kawano M, Yamada K, Matsui S, Saeki T, Kamisawa T, Yamamoto M, Hamano H, Origuchi T, Hirata S, Tanaka Y, Tsuboi H, Sumida T, Okazaki K, Tanaka M, Chiba T, Mimori T, Umehara H.
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Journal Title
Mod Rheumatol.
Volume: 11
Pages: 1-7
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical implications of elevated serum interleukin-6 in IgG4-related disease.2019
Author(s)
Tsukuda S, Ikeura T, Ito T, Nakamaru K, Masuda M, Hori Y, Ikemune M, Yanagawa M, Tanaka T, Tomiyama T, Yamaguchi T, Ando Y, Uchida K, Fukui T, Nishio A, Terasawa R, Tanigawa N, Okazaki K.
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Journal Title
PLoS One.
Volume: 15
Pages: e0227479.
DOI
Related Report
Peer Reviewed
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[Journal Article] Extracellular vesicles microRNA analysis in type 1 autoimmune pancreatitis: Increased expression of microRNA-21.2019
Author(s)
Nakamaru K, Tomiyama T, Kobayashi S, Ikemune M, Tsukuda S, Ito T, Tanaka T, Yamaguchi T, Ando Y, Ikeura T, Fukui T, Nishio A, Takaoka M, Uchida K, Leung PSC, Gershwin ME, Okazaki K.
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Journal Title
Pancreatology. 2020 Feb 21. pii: S1424-3903(20)30048-X.
Volume: pii: S1424-3903
Pages: 30048-X.
DOI
Related Report
Peer Reviewed
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[Journal Article] Risk Factors for Pancreatic Stone Formation in Type 1 Autoimmune Pancreatitis: A Long-term Japanese Multicenter Analysis of 624 Patients2018
Author(s)
Ito T, Kawa S, Matsumoto A, Kubota K, Kamisawa T, Okazaki K, Hirano K, Hirooka Y, Uchida K, Masuda A, Ohara H, Shimizu K, Arakura N, Masamune A, Kanno A, Sakagami J, Itoi T, Ito T, Ueki T, Nishino T, Inui K, Mizuno N, Yoshida H, Sugiyama M, Iwasaki E, Irisawa A, Shimosegawa T, Chiba T.
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Journal Title
Pancreas
Volume: 48
Pages: 49-54
DOI
Related Report
Peer Reviewed
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[Journal Article] Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey.2018
Author(s)
Notohara K, Kamisawa T, Uchida K, Zen Y, Kawano M, Kasashima S, Sato Y, Shiokawa M, Uehara T, Yoshifuji H, Hayashi H, Inoue K, Iwasaki K, Kawano H, Matsubayashi H, Moritani Y, Murakawa K, Oka Y, Tateno M, Okazaki K, Chiba T.
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Journal Title
Journal of gastroenterology
Volume: 53
Pages: 845-853
DOI
Related Report
Peer Reviewed
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[Journal Article] Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey.2018
Author(s)
Notohara K, Kamisawa T, Uchida K, Zen Y, Kawano M, Kasashima S, Sato Y, Shiokawa M, Uehara T, Yoshifuji H, Hayashi H, Inoue K, Iwasaki K, Kawano H, Matsubayashi H, Moritani Y, Murakawa K, Oka Y, Tateno M, Okazaki K, Chiba
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Journal Title
J Gastroenterol.
Volume: 印刷中
Pages: 印刷中
DOI
Related Report
Peer Reviewed
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[Journal Article] Morphological and immunohistochemical comparison of intrapancreatic nerves between chronic pancreatitis and type 1 autoimmune pancreatitis.2017
Author(s)
Kato K, Ikeura T, Yanagawa M, Tomiyama T, Fukui T, Uchida K, Takaoka M, Nishio A, Uemura Y, Satoi S, Yamada H, Okazaki K.
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Journal Title
Pancreatology
Volume: 17
Pages: 403-410
DOI
Related Report
Peer Reviewed
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[Journal Article] Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics.2017
Author(s)
Tanaka T, Zhang W, Sun Y, Shuai Z, Chida AS, Kenny TP, Yang GX, Sanz I, Ansari A, Bowlus CL, Ippolito GC, Coppel RL, Okazaki K, He XS, Leung PSC, Gershwin ME.
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Journal Title
Hepatology
Volume: 66
Pages: 885-895
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis.2017
Author(s)
Yanagawa M, Uchida K, Ando Y, Tomiyama T, Yamaguchi T, Ikeura T, Fukui T, Nishio A, Uemura Y, Miyara T, Okamoto H, Satoi S, Okazaki K.
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Journal Title
J Gastroenterol
Volume: 53
Pages: 449-460
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sclerosing Esophagitis with IgG4-positive Plasma Cell Infiltration.2017
Author(s)
Mori S, Tahashi Y, Uchida K, Ikeura T, Danbara N, Wakamatsu T, Kusuda T, Takahashi Y, Yanagawa M, Matsushita M, Ohe C, Michiura T, Inoue K, Kon M, Okazaki K.
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Journal Title
Intern Med.
Volume: 56
Pages: 3023-3026
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The role of basophils in the pathogenesis of type 1 autoimmune pancreatitis.2018
Author(s)
Kazushige Uchida, Masato Yanagawa, Tsukasa Ikeura, Toshihiro Tanaka, Takashi Tomiyama, Takashi Yamaguchi, Yugo Ando, Toshiro Fukui, Nishio Akiyoshi, Sohei Satoi, Kazuichi Okazaki
Organizer
Joint Meeting of the Asian-Oceanic Pancreatic Association, the Korean Pancreatobiliary Association, and Korean Pancreas Surgery Club 2018
Related Report
Int'l Joint Research
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