Immunologic response to Helicobacter involved in the development of chronic gastritis

• Project/Area Number: 20390207
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Norihiko Kyoto University, 医学研究科, 准教授 (50419446)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000); Fiscal Year 2010: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: 内科学 / 免疫学 / 細胞・組織 / 生体分子 / 感染症

Research Abstract

H. pylori CagA in the stomach plays an important role in the migration of H. pylori-primed CM4^+ T cells in the gastric mucosa from the Peyer's patches. In addition, H. pylori CagA can directly trigger epithelial cells to produce TSLP and TSLP-mediated DC activation may be involved in Th2 responses triggering B cell activation in H. pylori-induced gastritis.

Research Products

• [Journal Article] Dysregulated generation of follicular helper T cells in the spleen triggers fatal autoimmune hepatitis in mice. (2011)
  • Author(s): Aoki N, Kido M, Iwamoto S, Nishiura H, Maruoka R, Tanaka J, Watanabe T, Okazaki T, Chiba T, Watanabe N.
  • Journal Title: Gastroenterology. 140 Pages: 1322-1333
  • NAID: 120003001404
  • Peer Reviewed
• [Journal Article] Dysregulated generation of follicular helper T cells in the spleen triggers fatal autoimmune hepatitis in mice (2011)
  • Author(s): Aoki N, Kido M, Iwamoto S, Nishiura H, Maruoka R, Tanaka J, Watanabe T, Okazaki T, Chiba T, Watanabe N.
  • Journal Title: Gastroenterology Volume: 140 Pages: 1322-1333
  • NAID: 120003001404
  • Peer Reviewed
• [Journal Article] Helicobacter pylori promotes the production of thymic stromal lymphopoietin by gastric epithelial cells and induces dendritic cell-mediated inflammatory Th2 responses. (2010)
  • Author(s): Kido M, Tanaka J, Aoki N, Iwamoto S, Nishiura H, Chiba T, Watanabe N.
  • Journal Title: Infect Immun. 78 Pages: 108-114
  • Peer Reviewed
• [Journal Article] Proinflammatory Th2 cytokines induce production of thymic stromal lymphopoietin in human colonic epithelial cells. (2010)
  • Author(s): Tanaka J, Saga K, Kido M, Nishiura H, Akamatsu T, Chiba T, Watanabe N.
  • Journal Title: Dig Dis Sci. 55 Pages: 1896-1904
  • Peer Reviewed
• [Journal Article] Distinct signal codes generate dendritic cell functional plasticity. (2010)
  • Author(s): Arima K, Watanabe N, Hanabuchi S, Chang M, Sun SC, Liu YJ.
  • Journal Title: Sci Signal. 3(105)
  • Peer Reviewed
• [Journal Article] Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of forkhead box P3+ regulatory T cells in human thymus. (2010)
  • Author(s): Hanabuchi S, Ito T, Park WR, Watanabe N, Shaw JL Roman E, Arima K, Wang YH, VooKS, Cao W, Liu YJ.
  • Journal Title: J Immunol. 184 Pages: 2999-3007
  • Peer Reviewed
• [Journal Article] Analysis of Humoral Immune Response in Experimental Autoimmune Pancreatitis in Mice. (2010)
  • Author(s): Asada M, Nishio A, Akamatsu T, Tanaka J, Saga K, Kido M, Watanabe N, Uchida K, Fukui T, Okazaki K, Chiba T.
  • Journal Title: Pancreas. 39 Pages: 224-231
  • Peer Reviewed
• [Journal Article] Proinflammatory Th2 cytokines induce production of thymic stromal lymphopoietin in human colonic epithelial cells. (2010)
  • Author(s): Tanaka J, Saga K, Kido M, Nishiura H, Akamatsu T, Chiba T, Watanabe N
  • Journal Title: Dig Dis Sci. Volume: 55 Pages: 1896-1904
  • Peer Reviewed
• [Journal Article] Distinct signal codes generate dendritic cell functional plasticity (2010)
  • Author(s): Arima K, Watanabe N, Hanabuchi S, Chang M, Sun SC, Liu YJ.
  • Journal Title: Science Signaling (In press)
  • Peer Reviewed
• [Journal Article] Helicobacter pylori promotes the production of thymic stromal lymphopoietin by gastric epithelial cells and induces dendritic cell-mediated inflammatory Th2 responses (2010)
  • Author(s): Kido M, Tanaka J, Aoki N, Iwamoto S, Nishiura H, Chiba T, Watanabe N
  • Journal Title: Infection and Immunity 78 Pages: 108-114
  • Peer Reviewed
• [Journal Article] Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of forkhead box P3+ regulatory T cells in human thymus (2010)
  • Author(s): Hanabuchi S, Ito T, Park WR, Watanabe N, Shaw JL Roman E, Arima K, Wang YH, VooKS, Cao W, Liu YJ
  • Journal Title: Journal of Immunology 184 Pages: 2999-3007
  • Peer Reviewed
• [Journal Article] Analysis of humoral immune response in experimental autoimmune pancreatitis inmice (2010)
  • Author(s): Asada M, Nishio A, Akamatsu T, Tanaka J, Saga K, Kido M, Watanabe N, Uchida K, Fukui T, Okazaki K, Chiba T
  • Journal Title: Pancreas 39 Pages: 224-231
  • Peer Reviewed
• [Journal Article] Human TSLP and TLR3 ligand promote differentiation of Th17 cells with central memory phenotype under Th2- polarizing conditions. (2009)
  • Author(s): Tanaka J, Watanabe N, Kido M, Saga K, Akamatsu T, Nishio A, Chiba T
  • Journal Title: Clin Exp Allergy. 39 Pages: 89-100
  • Peer Reviewed
• [Journal Article] Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2^-polarizing conditions (2009)
  • Author(s): Tanaka J, Watanabe N, Kido M, Saga K, Akamatsu T, Nishio A, Chiba T
  • Journal Title: Clin Exp Allergy 39 Pages: 89-100
  • Peer Reviewed
• [Journal Article] Human TSLP directly enhances exansion of CD8+T cells (2009)
  • Author(s): Akaraatsu T, Watanabe N, Kido M, Saga K, Tanaka J, uzushima K., ishio A, Chiba T
  • Journal Title: Clin Exp Immunol 154 Pages: 98-106
  • Peer Reviewed
• [Journal Article] Human TSLP directly enhances expansion of CD8+ T cells. (2008)
  • Author(s): Akamatsu T, Watanabe N, Kido M, Saga K, Tanaka J, Kuzushima K, Nishio A, Chiba T.
  • Journal Title: Clin Exp Immunol. 154 Pages: 98-106
  • Peer Reviewed
• [Journal Article] Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling. (2008)
  • Author(s): Kido M, Watanabe N, Okazaki T, Akamatsu T, Tanaka J, Saga K, Nishio A, Honjo T, Chiba T.
  • Journal Title: Gastroenterology. 135 Pages: 1333-1343
  • Peer Reviewed
• [Journal Article] Mechanism for gastric cancer development by Helicobacter pylori infection. (2008)
  • Author(s): Chiba T, Marusawa H, Seno H, Watanabe N.
  • Journal Title: J Gatroenterol Hepatol 23 Pages: 1175-1181
• [Journal Article] Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling (2008)
  • Author(s): Kido M, Watanabe N, Okazaki T, Akamatsu T, Tanaka J, Saga K, Nishio A, Honjo T, Chiba T
  • Journal Title: Gastroenterology 135 Pages: 1333-1343
  • Peer Reviewed
• [Journal Article] Mechanism for gastric cancer development by Helicobacter pylori infection (2008)
  • Author(s): Chiba T, Marusawa H, Seno H, Watanabe N
  • Journal Title: J. Gastroenterol Hepatol 23 Pages: 1175-1181
• [Presentation] TNF-α but not IFN-γ plays a critical role in the development of fatal autoimmune hepatitis (2010)
  • Author(s): Watanabe N., Iwamoto S, Kido M, Aoki N, Nishiura H, Chiba T.
  • Organizer: United European Gastroenterology Week (UEGW)
  • Place of Presentation: Centre convencions intemacional Barcelona, Barcelona, Spain
  • Year and Date: 2010-10-26
• [Presentation] CCR6-CCL20 axis dependent direct migration of splenic CD4+ T cells is indispensable for the induction of fatal autoimmune hepatitis. (2010)
  • Author(s): Aoki N, Kido M, Iwamoto S, Nishiura H, Chiba T, Watanabe N.
  • Organizer: United European Gastroenterology Week (UEGW)
  • Place of Presentation: Centre convencions intemacional Barcelona, Barcelona, Spain
  • Year and Date: 2010-10-26
• [Presentation] 新規自己免疫性肝炎モデルの免疫病態解析からみた新たな治療戦略 (2010)
  • Author(s): 渡部則彦、岩本諭、木戸政博
  • Organizer: 第18回日本消化器関連学会週間
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-10-14
• [Presentation] 新規自己免疫性肝炎(AIH)モデルによるAIH発症機序の解析 (2010)
  • Author(s): 青木信裕, 木戸政博, 岩本諭, 西浦尚代, 丸岡隆太郎, 千葉勉, 渡部則彦
  • Organizer: 第93回日本消化器病学会近畿支部例会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2010-09-18
• [Presentation] Mechanisms involved in the development of fatal autoimmune hepatitis (2010)
  • Author(s): Watanabe N, Kido M, Aoki N, Iwamoto S, Nishiura H, Okazaki T, Honjo T, Chiba T
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-08-26
• [Presentation] Differential roles of PD-1 mediated signaling in inflammation in mouse models of Helicobacter infection and autoimmune gastritis. (2010)
  • Author(s): 木戸政博, 岩本諭, 青木信裕, 西浦尚代, 田中淳也, 千葉勉, 渡部則彦
  • Organizer: 第16回日本ヘリコバクター学会学術集会
  • Place of Presentation: 京都大学医学部芝蘭会館
  • Year and Date: 2010-06-24
• [Presentation] Differential roles of PD-1 mediated signaling in inflammation in mouse models of Helicobacter infection and autoimmune gastritis (2010)
  • Author(s): 木戸政博, 岩本諭, 青木信裕, 西浦尚代, 田中淳也, 千葉勉, 渡部則彦
  • Organizer: 第16回日本ヘリコバクター学会学術集会
  • Place of Presentation: 京都大学医学部芝蘭会館
  • Year and Date: 2010-06-24
• [Presentation] Regulatory T cells and PD-1-mediated signaling in AIH. (2010)
  • Author(s): 渡部則彦
  • Organizer: International Forum of the 96^<th> Annual Meeting of the Japanese Society of Gastroenterology
  • Place of Presentation: 新潟県新潟市朱鷺メッセ
  • Year and Date: 2010-04-24
• [Presentation] Regulatory T cells and PD-1-mediated signaling in AIH (2010)
  • Author(s): Watanabe N
  • Organizer: International Forum of the 96^<th> Annual Meeting of the Japanese Society of Gastroenterology
  • Place of Presentation: 新潟県新潟市朱鷺メッセ
  • Year and Date: 2010-04-24
• [Presentation] Regulatory roles of PD1 mediated signaling in the development of Helicobacter-induced gastritis and autoimmune gastritis (2009)
  • Author(s): 青木信裕、渡部則彦、千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-04
• [Presentation] TSLP regulates autoantibody production and inflammation in mouse models of autoimmune gastritis. (2009)
  • Author(s): 西浦尚代、渡部則彦、千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-04
• [Presentation] Regulatory roles of PD1 mediated signaling in the development of helicobacter-induced gastritis and autoimmune gastritis (2009)
  • Author(s): 青木信裕, 渡部則彦, 千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-04
• [Presentation] TSLP regulates autoantibody production and inflammation in mouse models of autoimmune gastritis (2009)
  • Author(s): 西浦尚代, 渡部則彦, 千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-04
• [Presentation] Differential roles of IFN-γ and TNF-α in the development of fatal autoimmune hepatitis (2009)
  • Author(s): 岩本諭, 渡部則彦, 千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-03
• [Presentation] Proinflammatory Th2 cytokines induce production of thymic stromal lymphopoietin in human colonic epithelial cells. (2009)
  • Author(s): 田中淳也、渡部則彦、千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] Essential role of CD8+ T cells in development of fatal autoimmune hepatitis (2009)
  • Author(s): 木戸政博, 渡部則彦, 千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] Proinflammatory Th2 cytokines induce production of thymic stromal lympho-poietin in human colonic epithelial cells (2009)
  • Author(s): 田中淳也, 渡部則彦, 千葉勉
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] 消化管 follicular lymphoma の診断と治療-その戦略 (2009)
  • Author(s): 渡部則彦, 近藤忠一, 千葉勉
  • Organizer: 第51回日本消化器病学会大会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-10-16
• [Presentation] 新規自己免疫性肝炎動物モデルにおける免疫担当細胞からみたその病態と治療の可能性 (2009)
  • Author(s): 渡部則彦, 木戸政博, 千葉勉
  • Organizer: 第51回日本消化器病学会大会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-10-14
• [Presentation] Role of Peyer's patches in H. pylori immunity. (2009)
  • Author(s): 渡部則彦
  • Organizer: XXIst International Workshop on Helicobacter and related bacteria in chronic digestive inflammation and gastric cancer
  • Place of Presentation: Fundacao Eng.Antonio de Almeida, Porto, Portugal
  • Year and Date: 2009-09-18
• [Presentation] Role of Peyer patches in H. pylori immunity (2009)
  • Author(s): 渡部則彦
  • Organizer: XXIst International Workshop on Helicobacter and related bacteria in chronic digestive inflammation and gastric cancer
  • Place of Presentation: Fundacao Eng. Antoniode Almeida, Porto, Portugal
  • Year and Date: 2009-09-18
• [Presentation] Helicobacter promote gastric epithelial cells to produce TSLP and induce DC-mediated inflammatory Th2 responses. (2009)
  • Author(s): Watanabe N, Kido M, Tanaka J, Chiba T.
  • Organizer: 米国消化器病週間(DDW)2009会議
  • Place of Presentation: Mccormick Place Convention Center, Chicago, USA.
  • Year and Date: 2009-06-02
• [Presentation] Helicobacter promote gastric epithelial cells to produce TSLP and induce DC-me diated inflammatory Th2 responses (2009)
  • Author(s): Watanabe N, Kido M, Tanaka J, Chiba T
  • Organizer: Digestive Disease Week and the 110^<th> Annual Meeting of the AGA institute
  • Place of Presentation: Mccormick Place Convention Center, Chicago, USA
  • Year and Date: 2009-06-02
• [Presentation] Essential role of dendritic cells in Peyer's patches in the development of Helicobacter-induced chronic gastritis (2008)
  • Author(s): 渡部則彦, 木戸政博, 千葉勉
  • Organizer: 国際樹状細胞会議2008
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-10-04
• [Presentation] Helicobacter pylori感染に対する宿主免疫応答でのTSLPの役割 (2008)
  • Author(s): 木戸政博、渡部則彦、千葉勉
  • Organizer: 第45回日本消化器免疫学会総会
  • Place of Presentation: 京都市京都メルパルク
  • Year and Date: 2008-07-03
• [Presentation] Helicobacter pylori感染に対する宿主免疫応答でのTSLPの役割 (2008)
  • Author(s): 木戸政博、渡部則彦、千葉勉
  • Organizer: 第14回日本ヘリコバクター学会学術集会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2008-06-27
• [Presentation] Helicobacter pylori感染に対する宿主免疫応答でのTSLPの役割 (2008)
  • Author(s): 木戸政博、渡部則彦、千葉勉
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2008-05-10
• [Book] H.pylori infection .The route from inflammation to cancer. In Sansonetti P, ed, Infection Biology Handbook Series. Bacterial Virulence. (2010)
  • Author(s): Chiba T, Marusawa H, Seno H, Watanabe N
  • Publisher: Basic principles, models and global approaches. Willey-Blackwell
• [Book] H.pylori infection-The route from inflammation to cancer. In Sansonetti P, ed, Infection Biology Handbook Series. Bacterial Virulence. Basic principles, models and global approaches. (2010)
  • Author(s): Chiba T, Marusawa H, Seno H, Watanabe N
  • Publisher: Willey-Blackwell