Immune regulation via intestinal autophagy for the treatment of Crohn's disease

• Project/Area Number: 19K08438
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nagahori Masakazu 東京医科歯科大学, 東京医科歯科大学病院, 准教授 (60420254)
• Co-Investigator(Kenkyū-buntansha): 永石 宇司 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (60447464) ; 渡辺 守 東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腸管免疫 / 腸管上皮 / 炎症性腸疾患 / オートファジー

Outline of Research at the Start

我々はこれまでの研究結果から、本研究では腸管粘膜の免疫恒常性は腸管上皮細胞のオートファジー機能と粘膜内リンパ球とのクロストークによって制御され、その破綻がIBDの本態となるという概念を提唱しつつ、大腸上皮特異的Atg5欠損マウス、大腸上皮細胞の初代(三次元)培養・移植技術、生体イメージング技術等々、我々が既に独自に樹立している技術を融合し、さらに上皮細胞のオートファジーによる腸管粘膜の新規免疫調節機構という新しい概念に着眼する。

Outline of Final Research Achievements

Inflammatory bowel disease (IBD) including Crohn’s disease is characterized by unrestrained lymphocyte activation that results in the production of a variety of pro-inflammatory cytokines as well as other mediators. Understanding the mechanisms of lymphocyte regulation is therefore of significant importance in the study of dysregulated mucosal inflammation such as IBD. Associated with this, several studies have revealed the importance of autophagy in several cell types of IBD pathology, such as intestinal epithelial cells. In this regard, we were able to observe ex vivo activities where functions of these lymphocytes can be modulated by autophagy in the epithelial cells derived from mouse intestines. Defining the physiological mechanisms of autophagy in intestinal epithelial cells will lead to a greater understanding of how manipulation of effecter lymphocyte function may provide insights into novel treatment of IBD.

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患(IBD)の新規治療法開発を困難にしている理由は、腸管の免疫調節機構が未だ不明確なことにある。本研究の意義は腸管の粘膜免疫応答に関する研究を独自に展開してきた申請者らが、マウス腸管組織由来の上皮細胞初代培養技術を応用しつつ腸管特有の免疫調節機構を繙くことで、これまで実現し得なかった「腸管上皮細胞オートファジーによる免疫応答調節機構」の解明に向けた技術基盤を樹立するという免疫学的貢献ばかりでなく、IBDにおける腸管粘膜傷害に対するその特異的な免疫調節異常を標的とした新規治療法の開発基盤の創出に発展するものと期待できる。

Research Products

• [Int'l Joint Research] Brigham and Women's Hospital/Harvard Medical School(米国)
• [Int'l Joint Research] Imperial College London(英国)
• [Journal Article] 外来クローン病患者における生体インピーダンス法を用いた体組成の評価 (2022)
  • Author(s): 斎藤 恵子, 太田 一樹, 長堀 正和, 藤井 俊光, 竹中 健人, 大塚和朗, 井津井 康浩, 篠原 夏美, 松下 由佳子, 岡本 隆一
  • Journal Title: 学会誌JASPEN Volume: 4 Pages: 35-43
  • Peer Reviewed
• [Journal Article] 【炎症性腸疾患の粘膜治癒を再考する】Crohn病における小腸粘膜治癒評価の意義 バルーン内視鏡の立場から (2022)
  • Author(s): 大塚 和朗, 竹中 健人, 齊藤 詠子, 日比谷 秀爾, 河本 亜美, 森川 亮, 藤井 俊光, 清水 寛路, 長堀 正和, 岡本 隆一
  • Journal Title: 胃と腸 Volume: 57 Pages: 173-181
• [Journal Article] Deep neural network for video colonoscopy of ulcerative colitis: a cross-sectional study (2022)
  • Author(s): Kento Takenaka, Toshimitsu Fujii, Ami Kawamoto, Kohei Suzuki, Hiromichi Shimizu, Chiaki Maeyashiki, Osamu Yamaji, Maiko Motobayashi, Akira Igarashi, Ryoichi Hanazawa, Shuji Hibiya, Masakazu Nagahori, Eiko Saito, Ryuichi Okamoto, Kazuo Ohtsuka, Mamoru Watanabe
  • Journal Title: Lancet Gastroenterol Hepatol Volume: 7 Issue: 3 Pages: 230-237
  • DOI: 10.1016/s2468-1253(21)00372-1
  • Peer Reviewed / Open Access
• [Journal Article] Nickel particles are present in Crohn's disease tissue and exacerbate intestinal inflammation in IBD susceptible mice. (2022)
  • Author(s): Hiroki Matsuda, Yoichi Nibe-Shirakihara, Akiko Tamura, Emi Aonuma, Satoko Arakawa, Kana Otsubo, Yasuhiro Nemoto, Takashi Nagaishi, Kiichiro Tsuchiya, Shigeomi Shimizu, Averil Ma, Mamoru Watanabe, Motohiro Uo, Ryuichi Okamoto, Shigeru Oshima.
  • Journal Title: Biochemical and Biophysical Research Communications. Volume: 592 Pages: 74-80
  • DOI: 10.1016/j.bbrc.2021.12.111
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activated mucosal-associated invariant T cells have a pathogenic role in a murine model of inflammatory bowel disease. (2022)
  • Author(s): usuke Yasutomi, Asako Chiba, Keiichi Haga, Goh Murayama, Ayako Makiyama, Taiga Kuga, Mamoru Watanabe, Ryuichi Okamoto, Akihito Nagahara, Takashi Nagaishi, Saichiko Miyake.
  • Journal Title: Cellular and Molecular Gastroenterology and Hepatology. Volume: 13 Issue: 1 Pages: 81-93
  • DOI: 10.1016/j.jcmgh.2021.08.018
  • Peer Reviewed / Open Access
• [Journal Article] 腸内細菌叢に対するIgAの重要性. (2022)
  • Author(s): 永石宇司.
  • Journal Title: 日本臨床腸内微生物学会誌. Volume: 24 Pages: 19-20
• [Journal Article] 【診断の決め手となった画像・所見II-消化器】消化管 クローン病の診断 (2021)
  • Author(s): 北詰 良雄, 竹中 健人, 藤井 俊光, 長堀 正和, 大塚 和朗
  • Journal Title: 臨床放射線 Volume: 66 Pages: 1491-1498
• [Journal Article] IBD診療現場のPros & Cons[No.3](その1) クローン病に対する生物学的製剤治療にチオプリン製剤を併用するか?併用するの立場から (2021)
  • Author(s): 長堀 正和
  • Journal Title: IBD Research Volume: 15 Pages: 177-180
• [Journal Article] 【最新の内視鏡を使いこなす】最新のスコープを使いこなす 小腸内視鏡 小腸内視鏡 オリンパス社内視鏡 (2021)
  • Author(s): 大塚 和朗, 竹中 健人, 日比谷 秀爾, 河本 亜美, 斎藤 詠子, 藤井 俊光, 長堀 正和, 清水 寛路, 岡本 隆一
  • Journal Title: 消化器内視鏡 Volume: 33 Pages: 1283-1287
• [Journal Article] Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus (2021)
  • Author(s): Hiromichi Shimizu, Toshimitsu Fujii, Kenji Kinoshita, Ami Kawamoto, Shuji Hibiya, Kento Takenaka, Eiko Saito, Masakazu Nagahori, Kazuo Ohtsuka, Mamoru Watanabe, Ryuichi Okamoto
  • Journal Title: BMC Gastroenterol Volume: 21 Issue: 1 Pages: 494-494
  • DOI: 10.1186/s12876-021-02043-6
  • Peer Reviewed / Open Access
• [Journal Article] Higher concentrations of cytokine blockers are needed to obtain small bowel mucosal healing during maintenance therapy in Crohn's disease (2021)
  • Author(s): Kento Takenaka, Ami Kawamoto, Shuji Hibiya, Kohei Suzuki, Toshimitsu Fujii, Maiko Motobayashi, Hiromichi Shimizu, Masakazu Nagahori, Eiko Saito, Ryuichi Okamoto, Mamoru Watanabe, Kazuo Ohtsuka
  • Journal Title: Aliment Pharmacol Ther Volume: 54 Issue: 8 Pages: 1052-1060
  • DOI: 10.1111/apt.16551
  • Peer Reviewed
• [Journal Article] Substantial Epstein-Barr virus reactivation in a case of severe refractory ulcerative colitis: a possible role in exacerbation (2021)
  • Author(s): Shu Kato, Hiromichi Shimizu, Shohei Tomii, Hitoshi Uchida, Ami Kawamoto, Shuji Hibiya, Maiko Motobayashi, Kento Takenaka, Toshimitsu Fujii, Eiko Saito, Masakazu Nagahori, Kazuo Ohtsuka, Mariko Negi, Takumi Akashi, Takatoshi Matsuyama, Yusuke Kinugasa & Mamoru Watanabe
  • Journal Title: Clinical Journal of Gastroenterology Volume: 14 Issue: 2 Pages: 584-588
  • DOI: 10.1007/s12328-020-01319-w
  • Peer Reviewed
• [Journal Article] A nationwide survey concerning the mortality and risk of progressing severity due to arterial and venous thromboembolism in inflammatory boweldisease in Japan (2021)
  • Author(s): Katsuyoshi Ando,Kenji Watanabe, Sakiko Hiraoka, Taku Kobayashi,Masakazu Nagahori, Hiroki Ikeuchi, Shingo Kato, Motohiro Esaki, Makoto Naganuma, Satoshi Motoya,Masayuki Saruta, Hideo Suzuki, Hiroshi Nakase, Toshiaki Shimizu,Masahiro Iizuka, Mamoru Watanabe, YasuoSuzuki, and Tadakazu Hisamatsu
  • Journal Title: J Gastroenterol . Volume: 56 Issue: 12 Pages: 1062-1079
  • DOI: 10.1007/s00535-021-01829-5
  • Peer Reviewed
• [Journal Article] Immunoglobulin A-specific deficiency induces spontaneous inflammation specifically in the ileum (2021)
  • Author(s): Nagaishi Takashi、Watabe Taro、Kotake Kunihiko、Kumazawa Toshihiko、Aida Tomomi、et al.
  • Journal Title: Gut Volume: 71 Issue: 3 Pages: 487-496
  • DOI: 10.1136/gutjnl-2020-322873
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production. (2021)
  • Author(s): Ai Minamidate, Michio Onizawa, Chikako Saito, Rie Hikichi, Tomoaki Mochimaru, Mai Murakami, Chiharu Sakuma, Takehito Asakawa, Yuichi Hiraoka, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Hiromasa Ohira, Ryuichi Okamoto, Mamoru Watanabe.
  • Journal Title: Biochemistry and Biophysics Reports. Volume: 27 Pages: 101065-101065
  • DOI: 10.1016/j.bbrep.2021.101065
  • Peer Reviewed / Open Access
• [Journal Article] Oral administration of D-serine prevents the onset and progression of colitis in mice. (2021)
  • Author(s): Takehito Asakawa, Michio Onizawa, Chikako Saito, Rie Hikichi, Daiki Yamada, Ai Minamidate, Tomoaki Mochimaru, Shun-ichiro Asahara, Yoshiaki Kido, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Hiromasa Ohira, Ryuichi Okamoto, Mamoru Watanabe.
  • Journal Title: Journal of Gastroenterolog. Volume: 56 Issue: 8 Pages: 732-745
  • DOI: 10.1007/s00535-021-01792-1
  • Peer Reviewed / Open Access
• [Journal Article] 免疫グロブリンAの欠損により回腸特異的な炎症が自然発症する. (2021)
  • Author(s): 安達貴弘，永石宇司.
  • Journal Title: 消化器学サイエンス. Volume: 5 Pages: 230-232
• [Journal Article] 5-aminosalicylate-intolerant patients are at increased risk of colectomy for ulcerative colitis (2021)
  • Author(s): Shuji Hibiya, Yusuke Matsuyama, Toshimitsu Fujii, Chiaki Maeyashiki, Eiko Saito, Kimiko Ito, Hiromichi Shimizu, Ami Kawamoto, Maiko Motobayashi, Kento Takenaka, Masakazu Nagahori, Masayuki Kurosaki, Tsunehito Yauchi, Kazuo Ohtsuka, Takeo Fujiwara, Ryuichi Okamoto, Mamoru Watanabe
  • Journal Title: Aliment Pharmacol Ther Volume: 53 Pages: 103-113
  • Peer Reviewed
• [Journal Article] Rapid prediction of 1-year efficacy of tofacitinib for treating refractory ulcerative colitis (2021)
  • Author(s): Hiromichi Shimizu, Toshimitsu Fujii, Shuji Hibiya, Maiko Motobayashi, Kohei Suzuki, Kento Takenaka, Eiko Saito, Masakazu Nagahori, Kazuo Ohtsuka, Mamoru Watanabe
  • Journal Title: Intest Res Volume: 19 Issue: 1 Pages: 115-118
  • DOI: 10.5217/ir.2020.00030
  • Peer Reviewed / Open Access
• [Journal Article] Week 2 Symptomatic Response with Vedolizumab as a Predictive Factor in Japanese Anti-TNFα-Naive Patients with Ulcerative Colitis: A post hoc Analysis of a Randomized, Placebo-Controlled Phase 3 Trial (2021)
  • Author(s): Masakazu Nagahori, Kenji Watanabe, Satoshi Motoya, Haruhiko Ogata, Takanori Kanai, Toshiyuki Matsui, Yasuo Suzuki, Philippe Pinton, Lyann Ursos, Shigeru Sakamoto, Mitsuhiro Shikamura, Tetsuharu Hori, Jovelle Fernandez, Toshifumi Hibi, Mamoru Watanabe
  • Journal Title: Digestion Volume: 15 Issue: 5 Pages: 1-11
  • DOI: 10.1159/000512235
  • Peer Reviewed / Open Access
• [Journal Article] Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal. (2021)
  • Author(s): Ryo Morikawa, Yasuhiro Nemoto, Yuki Yonemoto, Shohei Tanaka, Yuria Takei, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Kengo Nozaki , Tomohiro Mizutani, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto.
  • Journal Title: Cell Mol Gastroenterol Hepatol. Volume: 11 Issue: 5 Pages: 1483-1503
  • DOI: 10.1016/j.jcmgh.2021.01.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy and safety of a new vedolizumab subcutaneous formulation in Japanese patients with moderately to severely active ulcerative colitis (2020)
  • Author(s): Taku Kobayashi, Hiroaki Ito, Toshifumi Ashida, Tadashi Yokoyama, Masakazu Nagahori, Tomoki Inaba, Mitsuhiro Shikamura, Takayoshi Yamaguchi, Tetsuharu Hori, Philippe Pinton, Mamoru Watanabe, Toshifumi Hibi
  • Journal Title: Intest Res Volume: 18 Issue: 4 Pages: 448-460
  • DOI: 10.5217/ir.2020.00026
  • Peer Reviewed / Open Access
• [Journal Article] Pre-conception status, obstetric outcome and use of medications during pregnancy of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) in Japan: Multi-center retrospective descriptive study (2020)
  • Author(s): Sayaka Tsuda, Azusa Sameshima, Michikazu Sekine, Haruna Kawaguchi, Daisuke Fujita, Shintaro Makino, Akio Morinobu, Yohko Murakawa, Kiyoshi Matsui, Takao Sugiyama, Mamoru Watanabe, Yasuo Suzuki, Masakazu Nagahori, Atsuko Murashima, Tatsuya Atsumi, Kenji Oku, Nobuaki Mitsuda, Syuji Takei, Takako Miyamae, et al.
  • Journal Title: Mod Rheumatol Volume: 30 Issue: 5 Pages: 852-861
  • DOI: 10.1080/14397595.2019.1661592
  • Peer Reviewed
• [Journal Article] Nickel ions attenuate autophagy flux and induce transglutaminase 2 (TG2) mediated post-translational modification of SQSTM1/p62. (2020)
  • Author(s): Emi Aonuma, Akiko Tamura, Hiroki Matsuda, Takehito Asakawa, Yuriko Sakamaki, Kana Otsubo, Yoichi Nibe, Michio Onizawa, Yasuhiro Nemoto, Takashi Nagaishi, Kiichiro Tsuchiya, Tetsuya Nakamura, Motohiro Uo, Mamoru Watanabe, Ryuichi Okamoto, Shigeru Oshima.
  • Journal Title: Biochem Biophys Res Commun. Volume: 542 Pages: 17-23
  • DOI: 10.1016/j.bbrc.2021.01.023
  • Peer Reviewed / Open Access
• [Journal Article] CEACAM1 specifically suppresses B cell receptor signaling-mediated activation.. (2020)
  • Author(s): Naoya Tsugawa, Daiki Yamada, Taro Watabe, Michio Onizawa, Shuang Wang, Yasuhiro Nemoto, Shigeru Oshima, Takeshi Tsubata, Takahiro Adachi, Yohei Kawano, Mamoru Watanabe, Richard S. Blumberg, Ryuichi Okamoto, Takashi Nagaishi.
  • Journal Title: Biochem Biophys Res Commun. Volume: 535 Pages: 99-105
  • DOI: 10.1016/j.bbrc.2020.11.126
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Receptor-Interacting Protein Kinase 3 (RIPK3) inhibits autophagic flux during necroptosis in intestinal epithelial cells. (2020)
  • Author(s): Otsubo K, Maeyashiki C, Nibe Y, Tamura A, Aonuma E, Matsuda H, Kobayashi M, Onizawa M, Nemoto Y, Nagaishi T, Okamoto R, Tsuchiya K, Nakamura T, Torii S, Itakura E, Watanabe M, Oshima S.
  • Journal Title: FEBS letters Volume: 594 Issue: 10 Pages: 1586-1595
  • DOI: 10.1002/1873-3468.13748
  • Peer Reviewed / Open Access
• [Journal Article] Evidence-based diagnosis and clinical practice guidelines for intestinal Behçet's disease 2020 edited by intractable diseases, the Health and Labour Sciences Research Grants. (2020)
  • Author(s): Kenji Watanabe , Satoshi Tanida , Nagamu Inoue , Reiko Kunisaki , Kiyonori Kobayashi , Masakazu Nagahori , Katsuhiro Arai , Motoi Uchino , Kazutaka Koganei , Taku Kobayashi , Mitsuhiro Takeno , Fumiaki Ueno , Takayuki Matsumoto , Nobuhisa Mizuki , Yasuo Suzuki , Tadakazu Hisamatsu
  • Journal Title: J Gastroenterol. Volume: Epub ahead of print Issue: 7 Pages: 679-700
  • DOI: 10.1007/s00535-020-01690-y
  • Peer Reviewed
• [Journal Article] Development and validation of a deep neural network for accurate evaluation of endoscopic images from patients with ulcerative colitis. (2020)
  • Author(s): Kento Takenaka , Kazuo Ohtsuka , Toshimitsu Fujii , Mariko Negi , Kohei Suzuki , Hiromichi Shimizu , Shiori Oshima , Shintaro Akiyama , Maiko Motobayashi , Masakazu Nagahori , Eiko Saito , Katsuyoshi Matsuoka , Mamoru Watanabe
  • Journal Title: Gastroenterology Volume: Epub ahead of print Issue: 8 Pages: 2150-2157
  • DOI: 10.1053/j.gastro.2020.02.012
  • Peer Reviewed
• [Journal Article] CD8αα+ T cells show amoeboid shape and frequent morphological change in?vitro, and localize to small intestinal intraepithelial region in?vivo (2020)
  • Author(s): Takei Yuria、Nemoto Yasuhiro、Morikawa Ryo、Tanaka Shohei、Oshima Shigeru、Nagaishi Takashi、Okamoto Ryuichi、Tsuchiya Kiichiro、Nakamura Tetsuya、Watanabe Mamoru
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 523 Issue: 2 Pages: 328-335
  • DOI: 10.1016/j.bbrc.2019.12.021
  • Peer Reviewed / Open Access
• [Journal Article] High-fat diet-derived free fatty acids impair the intestinal immune system and increase sensitivity to intestinal epithelial damage (2020)
  • Author(s): Tanaka Shohei、Nemoto Yasuhiro、Takei Yuria、Morikawa Ryo、Oshima Shigeru、Nagaishi Takashi、Okamoto Ryuichi、Tsuchiya Kiichiro、Nakamura Tetsuya、Stutte Susanne、Watanabe Mamoru
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 522 Issue: 4 Pages: 971-977
  • DOI: 10.1016/j.bbrc.2019.11.158
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Indolent T cell lymphoproliferative disorder with villous atrophy in small intestinediagnosed by single-balloon enteroscopy. (2019)
  • Author(s): Takashi Nagaishi, Daiki Yamada, Kohei Suzuki, Ryosuke Fukuyo, Eiko Saito, Masayoshi Fukuda, Taro Watabe, Naoya Tsugawa, Kengo Takeuchi, Kouhei Yamamoto, Ayako Arai, Kazuo Ohtsuka, Mamoru Watanabe
  • Journal Title: Clin J Gastroenterol. Volume: in press Issue: 5 Pages: 434-440
  • DOI: 10.1007/s12328-019-00971-1
  • Peer Reviewed / Open Access
• [Journal Article] Small Bowel Healing Detected by Endoscopy in Patients With Crohn’s Disease After Treatment With Antibodies Against Tumor Necrosis Factor (2019)
  • Author(s): Takenaka Kento、Fujii Toshimitsu、Suzuki Kohei、Shimizu Hiromichi、Motobayashi Maiko、Hibiya Shuji、Saito Eiko、Nagahori Masakazu、Watanabe Mamoru、Ohtsuka Kazuo
  • Journal Title: Clinical Gastroenterology and Hepatology Volume: inpress Issue: 7 Pages: 1545-1552
  • DOI: 10.1016/j.cgh.2019.08.024
  • Peer Reviewed / Open Access
• [Journal Article] Predictors of mucosal healing during induction therapy in patients with acute moderate‐to‐severe ulcerative colitis (2018)
  • Author(s): Motobayashi Maiko、Matsuoka Katsuyoshi、Takenaka Kento、Fujii Toshimitsu、Nagahori Masakazu、Ohtsuka Kazuo、Iwamoto Fumihiko、Tsuchiya Kiichiro、Negi Mariko、Eishi Yoshinobu、Watanabe Mamoru
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: in press Issue: 6 Pages: 1004-1010
  • DOI: 10.1111/jgh.14565
  • Peer Reviewed
• [Presentation] The Lack of IgA spontaneously induces the inflammation only in the ileum. (2021)
  • Author(s): Daiki Yamada, Takahiro Adachi, Richard S. Blumberg, Ryuichi Okamoto, Takashi Nagaishi.
  • Organizer: The 50th Annual meeting of Japanese Society of Immunology
  • Int'l Joint Research
• [Presentation] A case of indolent T cell lymphoproliferative disorder of gastrointestinal tract with CCR4+ T cell infiltration. (2021)
  • Author(s): Daiki Yamada, Takashi Nagaishi, Eiko Saito, Masayoshi Fukuda, Ayako Arai, Ryuichi Okamoto.
  • Organizer: The 80th Annual meeting of Japanese Cancer Association
  • Int'l Joint Research
• [Presentation] BCR signaling-mediated activation in lymphoid tissues is regulated by the long isoform of CEACAM1. (2021)
  • Author(s): akashi Nagaishi, Naoya Tsugawa, Daiki Yamada, Mamoru Watanabe, Richard S. Blumberg, Ryuichi Okamoto.
  • Organizer: Annual meeting of American Gastroenterology Association, Digestive Disease Week
  • Int'l Joint Research
• [Presentation] 腸内細菌叢に対するIgAの重要性. (2021)
  • Author(s): 永石宇司.
  • Organizer: 第24回日本臨床腸内微生物学会総会学術集会
  • Invited
• [Presentation] 回腸に多発潰瘍を伴い診断に苦慮した腸管子宮内膜症の一例 (2021)
  • Author(s): 五月女 浩子, 河本 亜美, 小金井 一隆, 冨井 翔平, 竹中 健人, 日比谷 秀爾, 清水 寛路, 伊藤 剛, 水谷 知裕, 油井 史郎, 根本 泰宏, 藤井 俊光, 齊藤 詠子, 永石 宇司, 長堀 正和, 大塚 和朗, 岡本 隆一
  • Organizer: 第363回日本消化器病学会関東支部例会
• [Presentation] BCR-mediated activation in lymphoid tissues is regulated by Ceacam1. (2021)
  • Author(s): Takashi Nagaishi
  • Organizer: SMI Virtual Poster Hall
  • Int'l Joint Research / Invited
• [Presentation] 小腸難治性疾患の診断と治療の新知見 クローン病のバルーン内視鏡による小腸粘膜治癒評価 (2020)
  • Author(s): 竹中 健人, 大塚 和朗, 鈴木 康平, 日比谷 秀爾, 河本 亜美, 清水 寛路, 本林 麻衣子, 福田 将義, 藤井 俊光, 齊藤 詠子, 長堀 正和, 土屋 輝一郎, 渡辺 守, 岡本 隆一
  • Organizer: 第58回日本小腸学会学術集会
• [Presentation] 下部消化管内視鏡検査にてクローン病様所見を認めたスキルス胃癌の1例 (2020)
  • Author(s): 高橋 慶子, 竹中 健人, 三好 正人, 清水 寛路, 本林 麻衣子, 齊藤 詠子, 藤井 俊光, 長堀 正和, 大塚 和朗, 岡本 隆一
  • Organizer: 第663回日本内科学会関東地方会
• [Presentation] 5ASA不耐は潰瘍性大腸炎において予後不良である (2020)
  • Author(s): 藤井 俊光, 日比谷 秀爾, 前屋舗 千明, 齊藤 詠子, 竹中 健人, 清水 寛路, 長堀 正和, 大塚 和朗, 黒崎 雅之, 矢内 常人, 泉 並木, 渡辺 守
  • Organizer: 第106回日本消化器病学会
• [Presentation] 抗TNFα製剤治療が有効であった潰瘍性大腸炎術後に発症した壊疽性膿皮症の一例 (2020)
  • Author(s): 河崎 翔, 清水 寛路, 日比谷 秀爾, 本林 麻衣子, 竹中 健人, 油井 史郎, 根本 泰宏, 齊藤 詠子, 藤井 俊光, 岡田 英理子, 大島 茂, 岡本 隆一, 土屋 輝一郎, 永石 宇司, 長堀 正和, 大塚 和朗, 朝比奈 靖浩, 松山 貴俊, 加藤 恒平, 渡辺 守
  • Organizer: 第359回日本消化器病学会関東支部例会
• [Presentation] BCR signaling in lymphoid tissues regulated by the long isoform of Ceacam1. (2020)
  • Author(s): Takashi Nagaishi, Naoya Tsugawa, Daiki Yamada, Yudai Kojima, Michio Onizawa, Taro Watabe, Richard S. Blumberg, Mamoru Watanabe.
  • Organizer: FOCIS 2020
  • Int'l Joint Research
• [Presentation] 慢性大腸炎モデルにおけるAPLの発現解析. (2020)
  • Author(s): 山田大貴, 永石宇司, 津川直也, 小島裕大, 渡部太郎, 渡辺 守.
  • Organizer: 第48回日本臨床免疫学会総会
• [Presentation] A case of villous atrophy with CCR4+ T cell infiltration in the small intestine. (2020)
  • Author(s): Takashi Nagaishi, Daiki Yamada, Naoya Tsugawa, Taro Watabe, Eiko Saito, Masayoshi Fukuda, Ayako Arai, Kazuo Ohtsuka, Mamoru Watanabe.
  • Organizer: UEGW 2020
  • Int'l Joint Research
• [Presentation] BCR signaling in lymphoid tissues is regulated by the long isoform of Ceacam1. (2020)
  • Author(s): Takashi Nagaishi, Naoya Tsugawa, Daiki Yamada, Taro Watabe, Michio Onizawa, Yudai Kojima, Richard S. Blumberg, Mamoru Watanabe.
  • Organizer: MICS 2020
  • Int'l Joint Research
• [Presentation] B cell receptor signaling in lymphoid tissues may be regulated by CEACAM1. (2020)
  • Author(s): Takashi Nagaishi, Naoya Tsugawa, Daiki Yamada, Taro Watabe, Michio Onizawa, Mamoru Watanabe.
  • Organizer: European Crohn’s and Colitis Organization 2020
  • Int'l Joint Research
• [Presentation] IBDモデルにおける腸管二次リンパ組織の機能解析. (2020)
  • Author(s): 永石宇司、渡部太郎、渡辺 守
  • Organizer: 日本応用酵素協会「全身性炎症疾患の病因・病態に関する研究助成」 第9回研究発表会
• [Presentation] IgA-deficiency causes spontaneous enteritis. (2019)
  • Author(s): Takahiro Adachi, Taro Watabe, Takashi Nagaishi, Mamoru Watanabe, Hajime Karasuyama, Soichiro Yoshikawa.
  • Organizer: 第48回日本免疫学会学術集会
  • Int'l Joint Research
• [Presentation] BCR signaling in the activated B cells may be regulated by the long isoform of Ceacam1. (2019)
  • Author(s): Naoya Tsugawa, Takashi Nagaishi, Daiki Yamada, Yudai Kojima, Taro Watabe, Shuang Wang, Michio Onizawa, Takahiro Adachi, Mamoru Watanabe.
  • Organizer: 第48回日本免疫学会学術集会
  • Int'l Joint Research
• [Presentation] 培養腸上皮幹細胞を用いた炎症性腸疾患に対する再生医療の開発 (2019)
  • Author(s): 高橋純一、川井麻央、平栗優衣、竹岡さや香、杉原ハディ優樹、永田紗矢香、竹中健人、齋藤詠子、福田将義、藤井俊光、長堀正和、油井史郎、土屋輝一郎、大塚和朗、渡辺 守
  • Organizer: 厚生労働科学研究費 難治性疾患政策研究事業 「難治性炎症性腸管障害に関する調査研究」令和元年度 第1回総会
• [Presentation] Analysis of ileocecal immune response in an animal model of colitis. (2019)
  • Author(s): Daiki Yamada, Takashi Nagaishi, Taro Watabe, Naoya Tsugawa, Yudai Kojima,Nisha Jose, Akinori Hosoya, Takahiro Adachi, Mamoru Watanabe.
  • Organizer: International Congress of Mucosal Immunology.
  • Int'l Joint Research
• [Presentation] Analysis of APL expression in an animal model of chronic colitis (2019)
  • Author(s): Takashi Nagaishi, Yudai Kojima, Taro Watabe, Naoya Tsugawa, Daiki Yamada, Nisha Jose, Akinori Hosoya, Masahiro Suzuki, Michio Onizawa, Mamoru Watanabe.
  • Organizer: Federation of Clinical Immunology Societies.
• [Presentation] APL downregulation in an animal model of chronic colitis. (2019)
  • Author(s): Daiki Yamada, Takashi Nagaishi, Yudai Kojima, Taro Watabe, Naoya Tsugawa, Nisha Jose, Akinori Hosoya, Masahiro Suzuki, Michio Onizawa, Mamoru Watanabe.
  • Organizer: Asian Organization of Crohn’s and Colitis
  • Int'l Joint Research
• [Presentation] Small bowel endoscopic healing of Crohn’s disease treated with anti-TNF antibodies. (2019)
  • Author(s): Kento Takenaka, Kazuo Ohtsuka, Toshimitsu Fujii, Kohei Suzuki, Hiromichi Shimizu, Maiko Motobayashi, Shuji Hibiya, Eiko Saito, Masakazu Nagahori, Mamoru Watanabe
  • Organizer: Asian Organization of Crohn’s and Colitis
  • Int'l Joint Research
• [Presentation] The clinical efficacy of ustekinumab (UST) in patients with Crohn’s disease (CD). (2019)
  • Author(s): Eiko Saito, Kohei Suzuki, Shuuji Hibiya, Maiko Motobayashi, Kento Takenaka, Nobukatsu Horita, Hiromichi Shimizu, Michio Onizawa, Toshimitsu Fujii, Masakazu Nagahori, Kazuo Ohtsuka, Mamoru Watanabe
  • Organizer: Asian Organization of Crohn’s and Colitis
  • Int'l Joint Research
• [Presentation] 潰瘍性大腸炎罹患粘膜に発生した腫瘍性病変に対するESDの検討. (2019)
  • Author(s): 福田将義、永石宇司、根木真理子、大塚和朗、渡辺 守.
  • Organizer: 第108回日本消化器内視鏡学会関東支部例会
• [Presentation] 慢性大腸炎モデルのT細胞におけるAPLの発現抑制. (2019)
  • Author(s): 山田大貴、永石宇司、津川直也、小島裕大、渡部太郎、鈴木雅博、鬼沢道夫、細谷明徳、Jose, Nisha、渡辺 守.
  • Organizer: 第105回日本消化器病学会総会
• [Presentation] APL expression is downregulated in an animal model of chronic colitis. (2019)
  • Author(s): Takashi Nagaishi, Yudai Kojima, Daiki Yamada, Taro Watabe, Naoya Tsugawa, Nisha Jose, Michio Onizawa, Mamoru Watanabe.
  • Organizer: European Crohn’s and Colitis Organization
  • Int'l Joint Research
• [Presentation] 慢性大腸炎モデルにおけるAPL発現の解析. (2019)
  • Author(s): 山田大貴、永石宇司、小島裕大、渡部太郎、津川直也、細谷明徳、Jose, Nisha、鈴木雅博、鬼沢道夫、渡辺 守.
  • Organizer: 第15回日本消化管学会総会学術集会
• [Patent(Industrial Property Rights)] 炎症性腸疾患の治療方法およびそれに用いるための医薬組成物 (2020)
  • Inventor(s): 永石 宇司
  • Industrial Property Rights Holder: 永石 宇司
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-554239
  • Filing Date: 2020
  • Acquisition Date: 2020
• [Patent(Industrial Property Rights)] 炎症性腸疾患の治療方法およびそれに用いるための医薬組成物 (2019)
  • Inventor(s): 永石宇司
  • Industrial Property Rights Holder: 永石宇司
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019