The role of basophils in type 1 autoimmune pancreatitis.

• Project/Area Number: 15K09052
• 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: UCHIDA Kazushige 関西医科大学, 医学部, 准教授 (40411516)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 自己免疫性膵炎 / IgG4 / 好塩基球 / M2マクロファージ / 自然免疫 / IgG4関連疾患 / １型自己免疫性膵炎 / M２マクロファージ

Outline of Final Research Achievements

Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. We investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP.
Basophils were detected in pancreatic tissues in 10 of 13 patients with type 1 AIP. Stimulation of TLR2 and/or TLR4, which were expressed on basophils in the pancreas, activated basophils in peripheral blood.In flow cytometric analysis, the ratios of basophils activated by TLR4 stimulation in type 1 AIP and atopic dermatitis were significantly higher than those in healthy subjects. Levels of basophils activated by TLR2 stimulation were higher in seven cases with type 1 AIP cases.Basophils activated via TLR 4 (or 2) signaling may play an important role in the pathophysiology of type 1 AIP.

Research Products

• [Journal Article] Clinical and pathophysiological aspects of type 1 autoimmune pancreatitis. (2018)
  • Author(s): Uchida K, Okazaki K.
  • Journal Title: J Gastroenterol. Volume: 53 Issue: 4 Pages: 475-483
  • DOI: 10.1007/s00535-018-1440-8
  • Peer Reviewed / Open Access
• [Journal Article] Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis. (2018)
  • 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.
  • Journal Title: J Gastroenterol. Volume: 53 Issue: 3 Pages: 449-460
  • DOI: 10.1007/s00535-017-1390-6
  • Peer Reviewed / Open Access
• [Journal Article] Smad2/3 Linker Phosphorylation Is a Possible Marker of Pancreatic Stem/Progenitor Cells in the Regenerative Phase of Acute Pancreatitis. (2017)
  • Author(s): Sakao M, Sakaguchi Y, Suzuki R, Takahashi Y, Kishimoto M, Fukui T, Uchida K, Nishio A, Matsuzaki K, Okazaki K.
  • Journal Title: Pancreas Volume: 2017 Issue: 5 Pages: 605-613
  • DOI: 10.1097/mpa.0000000000000759
  • Peer Reviewed
• [Journal Article] Roles of Regulatory T and B Cells in IgG4-Related Disease. (2017)
  • Author(s): Uchida K, Okazaki K.
  • Journal Title: Curr Top Microbiol Immunol. Volume: 401 Pages: 93-114
  • DOI: 10.1007/82_2016_41
  • ISBN: 9783319525419, 9783319525426
  • Acknowledgement Compliant
• [Journal Article] Clinical and pathophysiological issues associated with type 1 autoimmune pancreatitis. (2016)
  • Author(s): Uchida K, Miyoshi H, Ikeura T, Shimatani M, Takaoka M, Okazaki K.
  • Journal Title: Clin J Gastroenterol. Volume: 9 Issue: 1 Pages: 7-12
  • DOI: 10.1007/s12328-016-0628-9
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [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] 自己免疫性膵炎の診断について 診断基準の変遷と診断の現状 (2015)
  • Author(s): 内田 一茂, 岡崎 和一
  • Journal Title: 日本臨床免疫学会雑誌 Volume: 38 Issue: 7 Pages: 127-134
  • DOI: 10.4049/jimmunol.1500971
  • NAID: 130005089220
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Kazushige Uchida and Kazuichi Okazaki (2017)
  • Author(s): The role of innate immunity in type 1 AIP.
  • Organizer: 3rd International Symposium on IgG4-RD and Fibrosis
  • Place of Presentation: ウェスティンマウイ（ハワイ、アメリカ）
  • Year and Date: 2017-02-15
  • Int'l Joint Research
• [Presentation] Immunological Aspects in Type 1 Autoimmune Pancreatitis. (2017)
  • Author(s): Kazushige Uchida, Kazuichi Okazaki
  • Organizer: International Pancreatic Research Forum 2017
  • Int'l Joint Research
• [Presentation] １型自己免疫性膵炎の膵組織・末梢血における好塩基球の検討 (2017)
  • Author(s): 内田一茂、柳川雅人、池宗真美、津久田諭、三好秀明、池浦 司、島谷昌明、福井寿朗、高岡 亮、西尾彰功、岡崎和一
  • Organizer: 第54回日本消化器免疫学会総会
• [Presentation] 1型自己免疫性膵炎における活性化好塩基球の検討 (2017)
  • Author(s): 柳川雅人, 内田一茂, 岡崎和一
  • Organizer: 第48回日本膵臓学会大会
• [Presentation] Immunological Roles in Type 1 Autommune Pancreatitis (2017)
  • Author(s): 内田一茂
  • Organizer: 第48回日本膵臓学会大会
• [Presentation] 1型自己免疫性膵炎における好塩基球の検討 (2017)
  • Author(s): 内田一茂、柳川雅人、池宗真美、津久田諭、池浦司、山口隆志、富山尚、安藤祐吾、福井寿朗、西尾彰功、三好秀明、島谷昌明、高岡亮、里井壮平、岡崎和一
  • Organizer: 第34回日本胆膵病態・生理研究会
• [Presentation] Immunological Aspects in Type1 Autoimmune Pancreatitis. (2017)
  • Author(s): Kazushige Uchida and Kazuichi Okazaki
  • Organizer: 第103回日本消化器病学会総会
• [Presentation] 1型自己免疫性膵炎における好塩基球の関与 (2017)
  • Author(s): 柳川雅人、内田一茂、池宗真美、津久田諭、三好秀明、池浦 司、島谷昌明、福井寿郎、高岡 亮、西尾彰功、岡崎和一
  • Organizer: 第9回IgG4研究会
  • Place of Presentation: シスメックスホール（神戸）
• [Presentation] Analysis of Neutrophil Infiltration in Type 1 and Type2 Autoimmune Pancreatitis. (2016)
  • Author(s): K Uchida, T Mitsuyama, M Yanagawa, H Miyoshi, T Ikeura, M Shimatani, T Fukui, M Takaoka, A Nishio, N Mizuno, K Notohara, G Zamboni, L Frulloni, T Shimosegawa, K Okazaki.
  • Organizer: Joint meeting of IAP, JPS and AOPA
  • Place of Presentation: 仙台国際センター（仙台）
  • Year and Date: 2016-08-04
  • Int'l Joint Research
• [Presentation] 自己免疫性膵炎の病態と臨床的課題 (2016)
  • Author(s): 内田一茂、岡崎和一
  • Organizer: 第33回日本胆膵病態・生理研究会
  • Place of Presentation: 新大阪ワシントンプラザホテル
  • Invited
• [Presentation] １型・２型自己免疫性膵炎における好中球浸潤の差異についての検討 (2016)
  • Author(s): 内田一茂、光山俊行、柳川雅人、池宗真美、津久田諭、三好秀明、池浦 司、島谷昌明、高岡 亮、西尾彰功、水野伸匡、Giuseppe Zamboni、Luca Frulloni、能登原憲司、里井壮平、岡崎和一
  • Organizer: 第33回日本胆膵病態・生理研究会
  • Place of Presentation: 新大阪ワシントンプラザホテル
• [Presentation] 自己免疫性膵炎（1型・２型）における好中球浸潤機序の違いについて (2016)
  • Author(s): 内田一茂、光山俊行、柳川雅人、池宗真美、津久田諭、三好秀明、池浦 司、島谷昌明、高岡 亮、西尾彰功、水野伸匡、Giuseppe Zamboni、Luca Frulloni、能登原憲司、岡崎和一
  • Organizer: 第53回日本消化器免疫学会総会
  • Place of Presentation: ホテルニューオータニ大阪（大阪）
• [Presentation] The Pathophysiological Role of Toll-like Receptor Signaling in Type 1 Autoimmune Pancreatitis. (2015)
  • Author(s): K Uchida, Y Fukui, T Mitsuyama, H Miyoshi, T Ikeura, M Shimatani, T Fukui, M Matsushita, M Takaoka, A Nishio, K Okazaki.
  • Organizer: Asian Pasific Digestve Week 2015
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] The Difference in Mechanisms of Neutrophil Infiltration between Type 1 and Type2 Autoimmune Pancreatitis. (2015)
  • Author(s): K Uchida, T Mitsuyama, M Yanagawa, H Miyoshi, T Ikeura, M Shimatani, T Fukui, M Takaoka, A Nishio, N Mizuno, K Notohara, G Zamboni, L Frulloni, T Shimosegawa, K Okazaki.
  • Organizer: Annual Meeting of American Pancreatic Association.
  • Place of Presentation: SanDiego, USA
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] IgG4関連疾患（特に１型自己免疫性膵炎）におけるB細胞の役割 (2015)
  • Author(s): 内田一茂、岡崎和一
  • Organizer: 第４３回日本臨床免疫学会総会
  • Place of Presentation: 神戸国際会議場（兵庫、神戸）
  • Year and Date: 2015-10-22
• [Presentation] 1型自己免疫性膵炎におけるToll-like receptorからみた自然免疫の関与 (2015)
  • Author(s): 内田一茂、福井由理、岡崎和一
  • Organizer: 第24回日本シェーグレン学会
  • Place of Presentation: 京王プラザホテル（東京、新宿）
  • Year and Date: 2015-09-10
• [Presentation] Analysis of Innate Immune Response in Type 1 Autoimmune Pancreatitis. (2015)
  • Author(s): K Uchida, Y Fukui, T Mitsuyama, M Yanagawa, H Miyoshi, T Ikeura, Y Sakaguchi, M Shimatani, T Fukui, M Takaoka, A Nishio, K Okazaki.
  • Organizer: PCCA & IAP 2015
  • Place of Presentation: Shanghai, China
  • Year and Date: 2015-08-27
  • Int'l Joint Research
• [Presentation] １型自己免疫性膵炎におけるToll-like receptor発現とその陽性細胞に関する検討 (2015)
  • Author(s): 内田一茂、福井由理、池宗真美、柳川雅人、光山俊之、住本喜美、楠田武生、三好英明、小藪雅樹、池浦 司、島谷昌明、福井寿朗、高岡 亮、西尾彰功、岡崎和一
  • Organizer: 第52回消化器免疫学会
  • Place of Presentation: 京王プラザホテル（東京、新宿）
  • Year and Date: 2015-07-30
• [Presentation] 自己免疫性膵炎治療の現状と課題 当院における自己免疫性膵炎の治療 (2015)
  • Author(s): 内田 一茂, 高岡 亮, 岡崎 和一
  • Organizer: 第46回日本膵臓学会大会
  • Place of Presentation: 名古屋国際会議場（愛知、名古屋）
  • Year and Date: 2015-06-19
• [Presentation] １型自己免疫性膵炎における自然免疫の関与 (2015)
  • Author(s): 内田一茂、福井由理、光山俊行、柳川雅人、住本喜美、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32回日本胆膵病態・生理研究会
  • Place of Presentation: 京王プラザホテル（東京、新宿）
  • Year and Date: 2015-06-14
• [Presentation] 当院におけるIgG4関連硬化性胆管炎の治療 (2015)
  • Author(s): 内田一茂、高岡 亮、岡崎和一
  • Organizer: 第101回日本消化器病学会総会
  • Place of Presentation: 仙台国際センター（宮城、仙台）
  • Year and Date: 2015-04-25
• [Presentation] １型自己免疫性膵炎におけるM2マクロファージとTLRについて (2015)
  • Author(s): 内田一茂、福井由理、岡崎和一
  • Organizer: 第101回日本消化器病学会総会
  • Place of Presentation: 仙台国際センター（宮城、仙台）
  • Year and Date: 2015-04-25