The mechanism of IgG4 production and the role of innate immunity in type 1 AIP.

• Project/Area Number: 24591020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kansai Medical University
• Principal Investigator: KAZUSHIGE Uchida 関西医科大学, 医学部, 講師 (40411516)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: １型自己免疫性膵炎 / IgG4 / ２型自己免疫性膵炎 / 自己免疫性膵炎

Outline of Final Research Achievements

I focused on pathophysiology of type1 and type2 autoimmune pancreatitis using this grant. We found mainly three data about autoimmune pancreatitis. Firstly, CD19+CD24highCD38high Bregs seemed to increase reactively to suppress the disease activity. On the other hand, CD19+CD24highCD27+ Bregs might be involved in the development of type 1 AIP, although it still remains unclear whether the decrease of CD19+CD24highCD27+ cells is cause or effect of AIP. Secondly, TLR7 might be a key pattern recognition receptors involved in the development of type 1 AIP including immunosuppressive effect, Th2 type immune response and fibrosis. Third one is that significantly increased neutrophil infiltration around the interlobular pancreatic duct in type2 autoimmune pancreatitis may depend on GCP-2.

Research Products

• [Journal Article] Comparison of neutrophil infiltration between type 1 and type 2 autoimmune pancreatitis. (2015)
  • Author(s): Mitsuyama T, Uchida K, Sumimoto K, Fukui Y, Ikeura T, Fukui T, Nishio A, Shikata N, Uemura Y, Satoi S, Mizuno N, Notohara K, Shimosegawa T, Zamboni G, Frulloni L, Okazaki K.
  • Journal Title: Pancreatology. Volume: Epub ahead of print Issue: 3 Pages: 271-280
  • DOI: 10.1016/j.pan.2015.03.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis. (2015)
  • Author(s): Fukui Y, Uchida K, Sakaguchi Y, Fukui T, Nishio A, Shikata N, Sakaida N, Uemura Y, Satoi S, Okazaki K.
  • Journal Title: J Gastroenterol. Volume: 50 Issue: 5 Pages: 435-44
  • DOI: 10.1016/j.pan.2014.04.029
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 自己免疫性膵炎の病態研究 (2014)
  • Author(s): 内田一茂、岡崎和一
  • Journal Title: 日本消化器病学会雑誌 Volume: 110 Pages: 1570-8
  • NAID: 130004678079
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Role of CD19+CD24highCD38high and CD19+CD24highCD27+ Regulatory B Cells in Patients with Type 1 Autoimmune Pancreatitis. (2014)
  • Author(s): Kimi Sumimoto, Kazushige Uchida, Takeo Kusuda, Toshiyuki Mitsuyama, Yutaku Sakaguchi, Toshiro Fukui, Mitsunobu Matsushita, Makoto Takaoka, Akiyoshi Nishio, Kazuichi Okazaki
  • Journal Title: Pancreatology Volume: in press Issue: 3 Pages: 193-200
  • DOI: 10.1016/j.pan.2014.02.004
  • Peer Reviewed / Open Access
• [Journal Article] Acquired immunity plays an important role in the development of murine experimental pancreatitis induced by alcohol and lipopolysaccharide. (2014)
  • Author(s): Nakayama S, Nishio A, Yamashina M, Okazaki T, Sakaguchi Y, Yoshida K, Fukui T, Uchida K, Okazaki K.
  • Journal Title: Pancreas. Volume: 43 Issue: 1 Pages: 28-36
  • DOI: 10.1097/mpa.0b013e3182a7c76b
  • Peer Reviewed
• [Journal Article] Possible Involvement of Foxp3(+) Regulatory T Cells in the Development of Immune-Mediated Pancreatitis in MRL/Mp Mice Treated with Polyinosinic:Polycytidylic Acid. (2013)
  • Author(s): Koyabu M, Uchida K, Sakaguchi Y, Fukata N, Kusuda T, Miyoshi H, Yoshida K, Sumimoto K, Mitsuyama T, Fukui T, Nishio A, Okazaki K.
  • Journal Title: Int J Rheumatol. Volume: 2013 Pages: 367325-30
  • DOI: 10.1155/2013/367325
  • Peer Reviewed
• [Journal Article] A proposal of a diagnostic algorithm with validation of International Consensus Diagnostic Criteria for autoimmune pancreatitis in a Japanese cohort. (2013)
  • Author(s): Sumimoto K, Uchida K, Mitsuyama T, Fukui Y, Kusuda T, Miyoshi H, Tomiyama T, Fukata N, Koyabu M, Sakaguchi Y, Ikeura T, Shimatani M, Fukui T, Matsushita M, Takaoka M, Nishio A, Okazaki K.
  • Journal Title: Pancreatology. Volume: 13(3) Issue: 3 Pages: 230-7
  • DOI: 10.1016/j.pan.2013.02.010
  • Peer Reviewed
• [Journal Article] The similarity of Type 1 autoimmune pancreatitis to pancreatic ductal adenocarcinoma with significant IgG4-positive plasma cell infiltration. (2013)
  • Author(s): Fukui Y, Uchida K, Sumimoto K, Kusuda T, Miyoshi H, Koyabu M, Ikeura T, Sakaguchi Y, Shimatani M, Fukui T, Matsushita M, Takaoka M, Nishio A, Shikata N, Sakaida N, Uemura Y, Satoi S, Kwon AH, Okazaki K.
  • Journal Title: J Gastroenterol. Volume: 48(6) Issue: 6 Pages: 751-61
  • DOI: 10.1007/s00535-012-0677-x
  • NAID: 10031184065
  • Peer Reviewed
• [Journal Article] Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of dextran sodium sulfate-induced colitis. (2013)
  • Author(s): Kurishima A, Inaba M, Sakaguchi Y, Fukui T, Uchida K, Nishio A, Nomura S, Okazaki K.
  • Journal Title: J Gastroenterol. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Establishment of a Serum IgG4 Cut-off Value for the Differential Diagnosis of IgG4-related Sclerosing Cholangitis- A Japanese Cohort. (2013)
  • Author(s): Ohara H, Nakazawa T, Kawa S, Kamisawa T, Shimosegawa T, Uchida K, Hirano K, Nishino T, Hamano H, Kanno A, Notohara K, Hasebe O, Muraki T, Ishida E, Naitoh I, Okazaki K.
  • Journal Title: J Gastroenterol Hepatol Volume: 28 Issue: 7 Pages: 1247-51
  • DOI: 10.1111/jgh.12248
  • Peer Reviewed
• [Journal Article] Current concept and diagnosis of IgG4-related disease in the hepato-bilio-pancreatic system. (2013)
  • Author(s): Okazaki K, Uchida K, Ikeura T, Takaoka M.
  • Journal Title: J Gastroenterol. Volume: 48(3): Issue: 3 Pages: 303-14
  • DOI: 10.1007/s00535-012-0744-3
  • NAID: 10031169203
  • Peer Reviewed
• [Journal Article] Toll-like receptor activation in basophils contributes to the development of IgG4-related disease. (2013)
  • Author(s): Watanabe T, Yamashita K, Sakurai T, et al
  • Journal Title: J Gastroenterol Volume: 48 Issue: 2 Pages: 247-253
  • DOI: 10.1007/s00535-012-0626-8
  • NAID: 10031156310
  • Peer Reviewed
• [Journal Article] Prevalence of IgG4-Related Disease in Japan Based on Nationwide Survey in 2009. (2012)
  • Author(s): Uchida K, Masamune A, Shimosegawa T, Okazaki K.
  • Journal Title: Int J Rheumatol. Volume: 2012 Pages: 358371-358371
  • DOI: 10.1155/2012/358371
  • Peer Reviewed
• [Journal Article] Comparative Study on Experimental Autoimmune Pancreatitis and Its Extrapancreatic Involvement in Mice. (2012)
  • Author(s): Yamashina M, Nishio A, Nakayama S, Okazaki T, Uchida K, Fukui T, Okazaki K.
  • Journal Title: Pancreas. Volume: 41 Issue: 8 Pages: 1255-62
  • DOI: 10.1097/mpa.0b013e31824a0e58
  • Peer Reviewed
• [Journal Article] Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012. (2012)
  • Author(s): Ohara H, Okazaki K, Tsubouchi H, Inui K, Kawa S, et al.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 19 Issue: 5 Pages: 536-42
  • DOI: 10.1007/s00534-012-0521-y
  • NAID: 10031039385
  • Peer Reviewed
• [Journal Article] Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin. (2012)
  • Author(s): Nakajima A, et al.
  • Journal Title: J Gastroenterol. Volume: 47 Issue: 9 Pages: 978-987
  • DOI: 10.1007/s00535-012-0564-5
  • Peer Reviewed
• [Journal Article] Activation of Toll-like receptors and NOD-like receptors is involved in enhanced IgG4 responses in autoimmune pancreatitis. (2012)
  • Author(s): Watanabe T, Yamashita K, Fujikawa S, Sakurai T, Kudo M, Shiokawa, M, Kodama Y, Uchida K, Okazaki K, Chiba T.
  • Journal Title: Arthritis & Rheumatism Volume: 64 Issue: 3 Pages: 914-24
  • DOI: 10.1002/art.33386
  • NAID: 40019474430
  • Peer Reviewed
• [Journal Article] Regulatory T cells in Type 1 autoimmune pancreatitis (2012)
  • Author(s): Uchida K
  • Journal Title: International journal of rheumatology Volume: 795,026 Pages: 726-32
  • DOI: 10.1155/2012/795026
  • Peer Reviewed
• [Presentation] 自己免疫性膵炎におけるToll like receptor発現についての検討 (2015)
  • Author(s): 内田一茂、福井由理、光山俊行、柳川雅人、住本貴美、楠田武生、三好秀明、小藪雅樹、池浦 司、島谷昌明、高岡 亮、岡崎和一
  • Organizer: 第８回IgG4研究会
  • Place of Presentation: 福岡（福岡リージェントホテル）
  • Year and Date: 2015-03-21
• [Presentation] The Role of Innate Immunity in the Pathogenesis of Type 1 Autoimmune Pancreatitis. (2014)
  • Author(s): K Uchida, Y Fukui, M Yanagawa, T Mitsuyama, K Sumimoto, T Ikeura, Y Sakaguchi, M Shimatani, T Fukui, M Matsushita, M Takaoka, A Nishio, S Satoi, AH Kwon, K Okazaki
  • Organizer: 45th Anniversary Meeting of American Pancreatic Association and Japan Pancreatic Society
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2014-11-05 – 2014-11-08
• [Presentation] 自己免疫性膵炎からみたIgG4関連疾患 (2014)
  • Author(s): 内田一茂、岡崎和一
  • Organizer: 第42回日本臨床免疫学会
  • Place of Presentation: 東京（新宿京王プラザホテル）
  • Year and Date: 2014-09-25 – 2014-09-28
• [Presentation] 各種自己免疫性膵炎診断基準の診断能と診断方法についての検討 (2014)
  • Author(s): 3.内田一茂、住本貴美、光山俊行、三好秀明、池浦 司、島谷昌明、高岡 亮、岡崎和一
  • Organizer: 第45回日本膵臓学会大会
  • Place of Presentation: 北九州（リーガロイヤルホテル小倉）
  • Year and Date: 2014-07-11 – 2014-07-13
• [Presentation] １型自己免疫性膵炎における制御性B細胞の役割 (2014)
  • Author(s): 内田一茂、住本貴美、西尾彰功、岡崎和一
  • Organizer: 第51回日本消化器免疫学会
  • Place of Presentation: 京都（芝蘭会館）
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] 自己免疫性膵炎における各種診断基準の診断能の検討と診断方法についての提唱 (2014)
  • Author(s): 内田一茂、住本貴美、光山俊行、三好秀明、池浦 司、島谷昌明、高岡 亮、岡崎和一
  • Organizer: 第31回日本胆膵生理機能研究会
  • Place of Presentation: 東京（コクヨホール）
  • Year and Date: 2014-06-14
• [Presentation] 自己免疫性膵炎の各種診断基準の評価に基づく診断アルゴリズムの提案 (2014)
  • Author(s): 内田一茂、住本貴美、岡崎和一
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京（東京国際フォーラム）
  • Year and Date: 2014-04-23 – 2014-04-26
• [Presentation] 当院における１型自己免疫性膵炎の診断アルゴリズムと各種診断基準についての検討 (2014)
  • Author(s): 内田一茂、住本貴美、光山俊行、塩見圭佑、池浦 司、島谷昌明、高岡 亮、岡崎和一
  • Organizer: 第111回日本内科学会総会
  • Place of Presentation: 東京（東京国際フォーラム）
  • Year and Date: 2014-04-11 – 2014-04-13
• [Presentation] Comparison of IgG4-positive Plasma Cell Infiltration Between Type 1 Autoimmune Pancreatitis and Pancreatic Ductal Adenocarcinoma Based On Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. (2014)
  • Author(s): Kazushige Uchida, Yuri Fukui, Toshiyuki Mitsuyama, Kimi Sumimoto, Tsukasa Ikeura, Yutaku Sakaguchi, Masaaki Shimatani, Toshiro Fukui, Mitsunobu Matsushita, Makoto Takaoka1, Akiyoshi Nishio, Kazuichi Okazaki
  • Organizer: The International Symposium on IgG4-RD and Associated Conditions
  • Place of Presentation: Honolulu, USA
• [Presentation] Circulating CD19+CD24hiCD38hi regulatory B Cells in patients with type 1 autoimmune pancreatitis (2014)
  • Author(s): Kimi Sumimoto, Kazushige Uchida, Toshiyuki Mitsuyama, Yuri Fukui, Takeo Kusuda, Hideaki Miyoshi, Norimasa Fukata, Masanori Koyabu, Yutaku Sakaguchi, Tsukasa Ikeura, Masaaki Shimatani, Toshiro Fukui, Mitsunobu Matsushita, Makoto Takaoka, Akiyoshi Nishio, and Kazuichi Okazaki.
  • Organizer: The International Symposium on IgG4-RD and Associated Conditions
  • Place of Presentation: Honolulu, USA
• [Presentation] Comparison of IgG4-positive Plasma Cell in Type 1 Autoimmune Pancreatitis and Pancreatic Ductal Adenocarcinoma. (2013)
  • Author(s): Kazushige Uchida, Yuri Fukui, Toshiyuki Mitsuyama, Kimi Sumimoto, Takeo Kusuda, Hideaki Miyoshi, Yutaku Sakaguchi, Masaaki Shimatani, Toshiro Fukui,Makoto Takaoka, Akiyoshi Nishio, Kazuichi Okazaki
  • Organizer: 44th Annual meeting of American Pancreatic Association
  • Place of Presentation: Maiami, USA
• [Presentation] Importance of endoscopic retrograde pancreatography in diagnosis of segmental/focal type 1 autoimmune pancreatitis. (2013)
  • Author(s): Kimi Sumimoto, Kazushige Uchida, Kazuichi Okazaki
  • Organizer: 第56回日本消化器病学会大会(JDDW2013)
  • Place of Presentation: 東京（グランドプリンスホテル高輪）
• [Presentation] Analysis of IgG4-positive Plasma Cell in Type 1 Autoimmune Pancreatitis and Pancreatic Cancer. (2013)
  • Author(s): Kazushige Uchida, Yuri Fukui, Toshiyuki Mitsuyama, Kimi Sumimoto, Takeo Kusuda, Hideaki Miyoshi, Yutaku Sakaguchi, Masaaki Shimatani, Toshiro Fukui, Makoto Takaoka, Akiyoshi Nishio, Kazuichi Okazaki
  • Organizer: APDW2013
  • Place of Presentation: Shanghai, China
• [Presentation] The Similarity of IgG4-positive Plasma Cell Infiltration in Type 1 Autoimmune Pancreatitis and Pancreatic Ductal Adenocarcinoma. (2013)
  • Author(s): Kazushige Uchida, Yuri Fukui, Toshiyuki Mitsuyama, Kimi Sumimoto, Takeo Kusuda, Hideaki Miyoshi, Yutaku Sakaguchi, Masaaki Shimatani, Toshiro Fukui, Makoto Takaoka, Akiyoshi Nishio, Kazuichi Okazaki
  • Organizer: IAP and KPBS 2013
  • Place of Presentation: Seoul, Korea
• [Presentation] Increased peripheral CD19+CD24hiCD38hi regulatory B Cells may be involved in the pathophysiology of type 1 autoimmune pancreatitis. (2013)
  • Author(s): Kimi Sumimoto, Kazushige Uchida, Toshiyuki Mitsuyama, Yuri Fukui, Takeo Kusuda, Hideaki Miyoshi, Norimasa Fukata, Masanori Koyabu, Yutaku Sakaguchi, Tsukasa Ikeura, Masaaki Shimatani, Toshiro Fukui, Mitsunobu Matsushita, Makoto Takaoka, Akiyoshi Nishio, and Kazuichi Okazaki
  • Organizer: DDW2013
  • Place of Presentation: Orland, USA
• [Presentation] IgG4関連包括診断基準からみた膵癌におけるIgG4陽性細胞浸潤に関する検討 (2013)
  • Author(s): 内田一茂、福井由理、光山俊行、住本貴美、三好秀明、池浦司、島谷昌明、高岡亮、里井壯平、權 雅憲、岡崎和一
  • Organizer: 第41回日本臨床免疫学会
  • Place of Presentation: 下関（海峡メッセ下関）
• [Presentation] 1型自己免疫性膵炎と膵癌の鑑別診断におけるIgG4陽性形質細胞に関する検討 (2013)
  • Author(s): 内田一茂、福井由理、岡崎和一
  • Organizer: JDDW2013：第55回日本消化器病学会大会
  • Place of Presentation: 東京（グランドプリンスホテル高輪）
• [Presentation] 膵癌と1型自己免疫性膵炎におけるIgG4陽性細胞浸潤に関する検討 (2013)
  • Author(s): 内田一茂、福井由理、光山俊行、住本貴美、三好秀明、池浦司、島谷昌明、高岡亮、里井壯平、權 雅憲、岡崎和一
  • Organizer: 第50回日本消化器免疫学会
  • Place of Presentation: 東京（ホテルグランドヒル市ヶ谷）
• [Presentation] 膵癌におけるIgG4陽性細胞浸潤に関する検討 (2013)
  • Author(s): 内田一茂、福井由理、光山俊行、住本貴美、三好秀明、池浦司、島谷昌明、高岡亮、里井壯平、權 雅憲、岡崎和一
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台（仙台国際センター）
• [Presentation] 自験例における自己免疫性膵炎の診断に関する検討 (2013)
  • Author(s): 内田一茂、住本貴美、岡崎和一
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台（仙台国際センター）
• [Presentation] 1型自己免疫性膵炎患者における制御性B細胞の検討 (2013)
  • Author(s): 住本貴美, 内田一茂, 光山俊行, 福井由理, 楠田武生, 三好秀明, 坂口雄沢, 池浦司, 島谷昌明, 高岡亮, 西尾彰功, 岡崎和一
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台（仙台国際センター）
• [Presentation] 膵癌におけるIgG4陽性形質細胞の検討 (2013)
  • Author(s): 内田 一茂，福井 由理，楠田 武生，三好 秀明，小藪 雅紀，池浦 司，島谷 昌明，高岡 亮，岡崎 和一
  • Organizer: 第110回日本内科学会講演会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] パネルディスカッション１：消化器領域におけるIgG4関連疾患の診断と治療～包括診断基準を受けて～ (2013)
  • Author(s): 内田一茂
  • Organizer: 第９９回日本消化器病学会総会
  • Place of Presentation: 鹿児島城山ホテル
• [Presentation] A case study of immunological differences between type 1 and type 2 AIP. (2012)
  • Author(s): Kazushige Uchida
  • Organizer: American Pancreatic Association
  • Place of Presentation: Maiami, USA
• [Presentation] Comparison of International Consensus Diagnostic Criteria and Major Diagnostic Criteria for Autoimmune Pancreatitis (2012)
  • Author(s): Kimi Sumimoto, Kazushige Uchida, et al.
  • Organizer: Digestive Disease Week (DDW) 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Recent Advances in Autoimmune Pancreatitis (2012)
  • Author(s): Kazushige Uchida
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 新宿京王プラザホテル
• [Presentation] IgG4関連胆膵疾患におけるICOS陽性制御性T細胞によるIgG4産生機序に関する検討 (2012)
  • Author(s): 内田一茂
  • Organizer: 第40回日本臨床免疫学会
  • Place of Presentation: 新宿京王プラザホテル
• [Presentation] 自験例よりみた自己免疫性膵炎の長期予後 (2012)
  • Author(s): 内田一茂
  • Organizer: 第43回日本膵臓学会大会
  • Place of Presentation: 山形メトロポリタンホテル
• [Presentation] IgG4関連肝胆膵疾患における制御性T細胞に関する検討 (2012)
  • Author(s): 内田一茂
  • Organizer: 第49回日本消化器免疫学会
  • Place of Presentation: 鹿児島城山ホテル
• [Presentation] IgG4関連胆・膵病変におけるIgG4産生機序と制御性T細胞の意義 (2012)
  • Author(s): 内田一茂
  • Organizer: 第109回日本内科学会講演会
  • Place of Presentation: 京都 みやこメッセ
• [Presentation] IgG4陽性細胞浸潤からみた膵癌と１型自己免疫性膵炎
  • Author(s): 内田一茂、福井由理、光山俊行、住本貴美、池浦司、島谷昌明、高岡亮、里井壯平、權 雅憲、岡崎和一
  • Organizer: 第30回日本胆膵病態・生理研究会
  • Place of Presentation: 仙台（ウェスティンホテル仙台）
• [Presentation] 膵癌におけるIgG4陽性形質細胞の検討
  • Author(s): 内田一茂
  • Organizer: 第７回IgG4研究会
  • Place of Presentation: 岡山国際交流センター
• [Presentation] IgG4関連疾患における性差について
  • Author(s): 内田一茂
  • Organizer: 第8回消化器病における性差医学・医療研究会
  • Place of Presentation: 京都 芝蘭会館