Elucidation of the interplay between oral bacteria and intestinal innate immunity using Paneth cells in organoid cultures

• Project/Area Number: 26462831
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hokkaido University
• Principal Investigator: Nakamura Kiminori 北海道大学, 先端生命科学研究院, 准教授 (80381276)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 自然免疫 / Paneth細胞 / α-defensin / αディフェンシン

Outline of Final Research Achievements

To clarify the relationship between oral bacteria and intestinal epithelia cells in terms of innate immunity, the aim of this study was to establish an evaluation system for intestinal innate immunity focused on Paneth cell α-defensin secretory functions.New analysis method for Paneth cell secretory functions using cultured organoids from mouse small intestine and newly developed sandwich ELISA for α-defensin were established.
These methods will contribute to clarifying links between oral bacteria and intestinal innate immunity.

Research Products

• [Journal Article] Paneth cell α-defensins and enteric microbiota in health and disease (2016)
  • Author(s): Nakamura K, Sakuragi N, Takakuwa A, Ayabe T.
  • Journal Title: Bioscience of Microbiota, Food and Health Volume: 35 Issue: 2 Pages: 57-67
  • DOI: 10.12938/bmfh.2015-019
  • NAID: 130005150071
  • ISSN: 2186-3342
  • Peer Reviewed
• [Journal Article] Efficient production of a correctly folded mouse α-defensin, cryptdin-4, by refolding during inclusion body solubilization. (2015)
  • Author(s): Tomisawa S, Sato Y, Kamiya M, Kumaki Y, Kikukawa T, Kawano K, Demura M, Nakamura K, Ayabe T, Aizawa T.
  • Journal Title: Protein Expr Purif. Volume: 112 Pages: 21-28
  • DOI: 10.1016/j.pep.2015.04.007
  • NAID: 120005820696
  • Peer Reviewed / Open Access
• [Journal Article] Decreased secretion of Paneth cell α-defensins in graft-versus-host disease. (2015)
  • Author(s): Eriguchi Y, Nakamura K, Hashimoto D, Shimoda S, Shimono N, Akashi K, Ayabe T, Teshima T
  • Journal Title: Transplant Infectious Disease Volume: 17 Issue: 5 Pages: 702-706
  • DOI: 10.1111/tid.12423
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pr1E11, a novel anti-TROP-2 antibody isolated by adenovirus-based antibody screening, recognizes a unique epitope. (2015)
  • Author(s): Ikeda M, Yamaguchi M, Kato K, Nakamura K, Shiina S, Ichikawa-Ando T, Misaka H, Myojo K, Nakamura K, Sugimoto Y, Hamada H.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 458 Pages: 877-882
  • Peer Reviewed
• [Journal Article] Bacterial cell wall components regulate adipokine secretion from visceral adipocytes (2015)
  • Author(s): Taira R,Yamaguchi S, Shimizu K,Nakamura K, Ayabe T,Taira T.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 56 Issue: 2 Pages: 149-154
  • DOI: 10.3164/jcbn.14-74
  • NAID: 130004879378
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Stiff Substrates Increase YAP-Signaling-Mediated Matrix Metalloproteinase-7 Expression (2015)
  • Author(s): A. Nukuda, C. Sasaki, S. Ishihara, T. Mizutani, K. Nakamura, T. Ayabe, K. Kawabata, and H. Haga
  • Journal Title: Oncogenesis Volume: 4 Issue: 9 Pages: e165-e165
  • DOI: 10.1038/oncsis.2015.24
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 腸上皮細胞の抗菌ペプチドによる自然免疫. (2015)
  • Author(s): 中村公則, 綾部時芳.
  • Journal Title: 臨床免疫・アレルギー科 Volume: 64 Pages: 20-25
• [Journal Article] Pr1E11, a novel anti-TROP-2 antibody isolated by adenovirus-based antibody screening, recognizes a unique epitope. (2015)
  • Author(s): Ikeda M, Yamaguchi M, Kato K, Nakamura K, Shiina S, Ichikawa-Ando T, Misaka H, Myojo K, Nakamura K, Sugimoto Y, Hamada H.
  • Journal Title: Biochem Biophys Res Commun Volume: 458(4) Pages: 877-882
  • Peer Reviewed
• [Journal Article] Development of a sensitive screening method for selecting monoclonal antibodies to be internalized by cells. (2014)
  • Author(s): Yamaguchi M, Nishii Y, Nakamura K, Aoki H, Hirai S, Uchida H, Sakuma Y, Hamada H.
  • Journal Title: Biochemical and Biophysical Research Communications. Volume: 454 Issue: 4 Pages: 600-603
  • DOI: 10.1016/j.bbrc.2014.10.133
  • Peer Reviewed
• [Presentation] クローン病モデルマウスSAMP1/YitFcの病態形成に伴うdysbiosisとα-defensinの高次構造異常との関連 (2016)
  • Author(s): 清水由宇, 中村公則, 吉井彩季, 菊池摩仁, 櫻木直也, 綾部時芳
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-12-01
• [Presentation] Enteroidを用いたPaneth細胞顆粒分泌反応の可視化解析による機序解明 (2016)
  • Author(s): 横井 友樹, 中村 公則, 櫻木 直也, 菊池 摩仁, 綾部 時芳
  • Organizer: 第12回日本食品免疫学会学術大会
  • Place of Presentation: 伊藤謝恩ホール（東京都・文京区）
  • Year and Date: 2016-11-09
• [Presentation] クローン病モデルマウスSAMP1/Yitの病態進行とq-defensinの分泌異常 (2015)
  • Author(s): 中村公則、櫻木直也、綾部時芳
  • 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（宮城県・仙台市）
  • Year and Date: 2015-04-25
• [Presentation] 同位体顕微鏡で小腸の吸収機能を視る． (2015)
  • Author(s): 櫻木直也、中村公則、綾部時芳、永田康祐、坂本直哉、圦本尚義
  • Organizer: 第6回安定同位元素イメージング技術による産業イノベーションシンポジウム
  • Place of Presentation: 北海道大学学術交流会館（北海道 札幌市）
  • Year and Date: 2015-03-02
• [Presentation] 抗菌ペプチドαディフェンシンによる腸内環境の恒常性制御と疾病． (2014)
  • Author(s): 綾部時芳、櫻木直也、中村公則
  • Organizer: 第20回日本エンドトキシン・自然免疫研究会
  • Place of Presentation: 順天堂大学（東京都 文京区）
  • Year and Date: 2014-12-05 – 2014-12-06
• [Presentation] 高脂肪食による肥満における抗菌ペプチドα-defensin分泌の関与． (2014)
  • Author(s): 川田綾香、中村公則、櫻木直也、綾部時芳
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県 横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 組織常在型M2マクロファージ細胞の培養系の確立と間葉系細胞への影響について． (2014)
  • Author(s): 藤岡明博、櫻木直也、中村公則、古澤和也、佐々木直樹、綾部時芳、福井彰雅
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県 横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Paneth細胞α-defensinによる腸内細菌叢制御と疾患との関連の解明． (2014)
  • Author(s): 中村公則、櫻木直也、綾部時芳
  • Organizer: 生理学研究所研究会「粘膜免疫学と膜輸送生理学の融合」
  • Place of Presentation: 自然科学研究機構 生理学研究所（愛知県 岡崎市）
  • Year and Date: 2014-10-27 – 2014-10-28
• [Presentation] 腸内細菌を制御するαディフェンシンから疾病を眺める． (2014)
  • Author(s): 綾部時芳、櫻木直也、中村公則
  • Organizer: 第51回日本消化器免疫学会総会
  • Place of Presentation: 京都大学医学部芝蘭会館（京都府 京都市）
  • Year and Date: 2014-07-10 – 2014-07-11