NK cell-mediated immune regulation for IBD treatment

• Project/Area Number: 20K08304
• 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: Fujii Toshimitsu 東京医科歯科大学, 医学部附属病院, 助教 (30547451)
• 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)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 免疫学 / 腸管免疫 / 消化器病学 / 炎症性腸疾患 / 免疫

Outline of Research at the Start

我々はこれまでの一貫して腸管粘膜における免疫寛容の誘導機構に注目してきた研究結果から、本研究計画では NK細胞サブセットによる細胞傷害活性を応用したクローン病に対する新規治療法開発を遂行する。本研究はNK細胞による病原性T細胞の制御機構という独自の概念に着目しつつ、NK細胞サブセットの機能解析法、培養技術・移植技術、三次元生体イメージング技術等、我々が独自に樹立している技術を融合し、得られる成果からクローン病新規治療法の開発基盤と技術基盤の樹立を目指した先駆的研究になると期待する。

Outline of Final Research Achievements

Inflammatory bowel disease (IBD), including Crohn’s disease, is characterized by unrestrained effecter T cell 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 critical in the study of dysregulated mucosal inflammation such as IBD. Associated with this, several studies have revealed the importance of natural killer (NK) cells in the pathogenesis of several autoimmune diseases. In this regard, we were able to observe ex vivo and in vivo activities of effecter T cells modulated by a subset of NK cells. Defining the physiological mechanisms of cytotoxicity by NK cells will lead to a greater understanding of how manipulating 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、NK細胞サブセットの免疫学的機能解析法、および培養技術をといった、これまでの技術と知見を統合しつつ腸管特有の免疫調節機構を繙くことで、これまで理解されていなかった「NK細胞サブセットによるエフェクターT細胞の抑制機能」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] University of British Columbia(カナダ)
• [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] Apelin expression is downregulated in T cells in a murine model of chronic colitis (2023)
  • Author(s): Yamada D、Kojima Yi、Hosoya A、Suzuki、Watabe T、Inoue T、Tsugawa N、Asakawa T、Yonemoto Y、Onizawa M、Nemoto Y、Oshima S、Shimonaka M、Kuba Ki、Ishida J、Fukamizu A、Penninger JM、Watanabe M、Okamoto R、Nagaishi T
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 647 Pages: 72-79
  • DOI: 10.1016/j.bbrc.2023.01.068
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Motility Mapping Quantification Using the Classical Optical Flow Algorithm for Small Bowel Crohn’s Disease: Comparison with Balloon-assisted Enteroscopy Findings (2023)
  • Author(s): Kitazume Yoshio、Takenaka Kento、Ohtsuka Kazuo、Ozawa Yasuo、Kimura Koichiro、Watanabe Ryosuke、Tsuchiya Junichi、Fujii Toshimitsu、Nagahori Masakazu、Watanabe Mamoru、Tateishi Ukihide
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 22 Issue: 3 Pages: 325-334
  • DOI: 10.2463/mrms.mp.2021-0037
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access
• [Journal Article] A case of venous stasis colitis possibly caused by eplerenone (2023)
  • Author(s): Eiko Saito, Kazuo Ohtsuka, Ami Kawamoto, Toshimitsu Fujii, Kento Takenaka, Shuji Hibiya, Hiromichi Shimizu, Masakazu Nagahori, Shohei Tomii, Ryuichi Okamoto
  • Journal Title: Clin J Gastroenterol. Volume: 16 Issue: 1 Pages: 69-72
  • DOI: 10.1007/s12328-022-01722-5
  • Peer Reviewed
• [Journal Article] Zranb1-mutant mice display abnormal colonic mucus production and exacerbation of DSS-induced colitis. (2022)
  • Author(s): Tamura A, Ito G, Matsuda H, Nibe-Shirakihara Y, Hiraoka Y, Kitagawa S, Hiraguri Y, Nagata S, Aonuma E, Otsubo K, Nemoto Y, Nagaishi T, Watanabe M, Okamoto R, Oshima S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 628 Pages: 147-154
  • DOI: 10.1016/j.bbrc.2022.08.046
  • Peer Reviewed
• [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] Serum Levels of Infliximab Biosimilar in a Child Delivered From a Mother Treated for Ulcerative Colitis (2022)
  • Author(s): Ami Kawamoto, Toshimitsu Fujii, Ryuji Mitani, Yasuhiro Suzuki, Tsunehito Yauchi, Ryuichi Okamoto
  • Journal Title: Inflamm Bowel Dis. Volume: 28 Issue: 8 Pages: 1298-1299
  • DOI: 10.1093/ibd/izac111
  • Peer Reviewed
• [Journal Article] Characteristics of adult patients newly diagnosed with Crohn’s disease: interim analysis of the nation-wide inception cohort registry study of patients with Crohn’s disease in Japan (iCREST-CD) (2022)
  • Author(s): Matsuoka Katsuyoshi、Fujii Toshimitsu、Okamoto Ryuichi、et al.
  • Journal Title: Journal of Gastroenterology Volume: 57 Issue: 11 Pages: 867-878
  • DOI: 10.1007/s00535-022-01907-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mucosal healing of small intestinal stricture is associated with improved prognosis post-dilation in Crohn's disease (2022)
  • Author(s): Shuji Hibiya, Kazuo Ohtsuka, Kento Takenaka, Ami Kawamoto, Yusuke Matsuyama, Yumi Udagawa, Maiko Motobayashi, Hiromichi Shimizu, Toshimitsu Fujii, Eiko Saito, Masakazu Nagahori, Ryuichi Okamoto, Mamoru Watanabe
  • Journal Title: BMC Gastroenterol. Volume: 22 Issue: 1 Pages: 218-218
  • DOI: 10.1186/s12876-022-02300-2
  • Peer Reviewed / Open Access
• [Journal Article] Hemorrhagic gastric ulcer in a patient with Behcet's disease successfully treated with infliximab (2022)
  • Author(s): Shun Fujiwara, Ami Kawamoto, Maiko Motobayashi, Shuji Hibiya, Kento Takenaka, Hiromichi Shimizu, Eiko Saito, Toshimitsu Fujii, Masakazu Nagahori, Daisuke Kawata, Natsuka Umezawa, Tadashi Hosoya, Shinsuke Yasuda, Kazuo Ohtsuka, Ryuichi Okamoto
  • Journal Title: DEN Open. Volume: 3 Issue: 1
  • DOI: 10.1002/deo2.196
  • Peer Reviewed / Open Access
• [Journal Article] Transmural remission characterized by high biologic concentrations demonstrates better prognosis in Crohn's disease (2022)
  • Author(s): Kento Takenaka, Ami Kawamoto, Yoshio Kitazume, Toshimitsu Fujii, Yumi Udagawa, Hiromichi Shimizu, Shuji Hibiya, Masakazu Nagahori, Kazuo Ohtsuka, Mamoru Watanabe, Ryuichi Okamoto
  • Journal Title: J Crohns Colitis. Volume: - Issue: 6 Pages: 855-862
  • DOI: 10.1093/ecco-jcc/jjac185
  • Peer Reviewed
• [Journal Article] Serum Leucine-Rich α2 Glycoprotein: A Novel Biomarker for Transmural Inflammation in Crohn's Disease (2022)
  • Author(s): Kento Takenaka, Yoshio Kitazume, Ami Kawamoto, Toshimitsu Fujii, Yumi Udagawa, Ryosuke Wanatabe, Hiromichi Shimizu, Shuji Hibiya, Masakazu Nagahori, Kazuo Ohtsuka, Hiroyuki Sato, Akihiro Hirakawa, Mamoru Watanabe, Ryuichi Okamoto
  • Journal Title: Am J Gastroenterol. Volume: - Issue: 6 Pages: 1028-1035
  • DOI: 10.14309/ajg.0000000000002127
  • Peer Reviewed
• [Journal Article] 直腸リンパ濾胞過形成様病変から潰瘍性大腸炎の典型像へ進展した1例 (2022)
  • Author(s): 11．大久保 栄高, 藤田 美貴子, 久礼 里江, 藤井 俊光, 冨井 翔平, 根木 真理子, 入江 宏, 畑 啓介.
  • Journal Title: Gastroenterological Endoscopy. Volume: 64 Pages: 262-269
  • Peer Reviewed
• [Journal Article] 最新のIBD病勢モニタリング 画像検査(CT、MRI、腸管超音波、小腸造影)の活用法. (2022)
  • Author(s): 1.藤井 俊光, 岡本 隆一
  • Journal Title: IBD Research. Volume: 16 Pages: 90-96
• [Journal Article] 炎症性腸疾患治療における外科と内科の接点 重症潰瘍性大腸炎に対する治療. (2022)
  • Author(s): 河本 亜美, 藤井 俊光, 岡本 隆一
  • Journal Title: 外科 Volume: 84 Pages: 1054-1059
• [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] Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease (2021)
  • Author(s): Suzuki K, Kakuta Y, Naito T, Takagawa T, Hanai H, Araki H, Sasaki Y, Sakuraba H, Sasaki M, Hisamatsu T, Motoya S, Matsumoto T, Onodera M, Ishiguro Y, Nakase H, et al.
  • Journal Title: Inflamm Bowel Dis Volume: - Issue: 1 Pages: 21-31
  • DOI: 10.1093/ibd/izab004
  • Peer Reviewed / Int'l Joint Research
• [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] Deep Neural Network Accurately Predicts Prognosis of Ulcerative Colitis Using Endoscopic Images (2021)
  • Author(s): Kento Takenaka, Kazuo Ohtsuka, Toshimitsu Fujii, Shiori Oshima, Ryuichi Okamoto, Mamoru Watanabe
  • Journal Title: Gastroenterology Volume: 160 Issue: 6 Pages: 2175-2177
  • DOI: 10.1053/j.gastro.2021.01.210
  • Peer Reviewed / Open Access
• [Journal Article] Concomitant use of an immunomodulator with ustekinumab as an induction therapy for Crohn's disease: A systematic review and meta-analysis (2021)
  • Author(s): Takeo Yoshihara, Shinichiro Shinzaki, Takahiro Amano, Hideki Iijima, Tetsuo Takehara, Nagamu Inoue, Motoi Uchino, Motohiro Esaki, Taku Kobayashi, Masayuki Saruta, Ken Sugimoto, Shiro Nakamura, Keisuke Hata, Fumihito Hirai, Sakiko Hiraoka, Toshimitsu Fujii, Minoru Matsuura, Katsuyoshi Matsuoka, Kenji Watanabe, et al
  • Journal Title: J Gastroenterol Hepatol Volume: 15 Issue: 7 Pages: 1744-1753
  • DOI: 10.1111/jgh.15401
  • Peer Reviewed
• [Journal Article] Intestinal cancer in patients with Crohn's disease: A systematic review and meta-analysis (2021)
  • Author(s): Motoi Uchino, Hiroki Ikeuchi, Keisuke Hata, Tomohiro Minagawa, Yuki Horio, Ryuichi Kuwahara, Shiro Nakamura, Kenji Watanabe, Masayuki Saruta, Toshimitsu Fujii, Taku Kobayashi, Ken Sugimoto, Fumihito Hirai, Motohiro Esaki, Sakiko Hiraoka, Katsuyoshi Matsuoka, Shinichiro Shinzaki, Minoru Matsuura, Nagamu Inoue, et al
  • Journal Title: J Gastroenterol Hepatol Volume: 36 Issue: 2 Pages: 329-336
  • DOI: 10.1111/jgh.15229
  • Peer Reviewed
• [Journal Article] Does anti-tumor necrosis factor alpha prevent the recurrence of Crohn's disease? Systematic review and meta-analysis (2021)
  • Author(s): Uchino M, Ikeuchi H, Hata K, Minagawa T, Horio Y, Kuwahara R, Nakamura S, Watanabe K, Saruta M, Fujii T, Kobayashi T, Sugimoto K, Hirai F, Esaki M, Hiraoka S, Matsuoka K, Shinzaki S, Matsuura M, Inoue N, Nakase H, Watanabe M.
  • Journal Title: J Gastroenterol Hepatol Volume: - Issue: 4 Pages: 864-872
  • DOI: 10.1111/jgh.15288
  • 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] Crohn disease: magnetic resonance enterocolonography features of endoscopic ulcer stages reclassified with the healing process and the relationships to prognoses (2021)
  • Author(s): Yoshio Kitazume, Kento Takenaka, Kazuo Ohtsuka, Koichiro Kimura, Yusuke Ogihara, Tomoyuki Fujioka, Junichi Tsuchiya, Toshimitsu Fujii, Mamoru Watanabe, Ukihide Tateisi
  • Journal Title: Jpn J Radiol Volume: 39 Issue: 5 Pages: 459-476
  • DOI: 10.1007/s11604-020-01082-5
  • NAID: 210000160272
  • Peer Reviewed
• [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 Issue: 1 Pages: 103-113
  • DOI: 10.1111/apt.16120
  • 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] 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] High b-value computed diffusion-weighted imaging for differentiating bowel inflammation in Crohn's disease (2020)
  • Author(s): Yoshio Kitazume, Junichi Tsuchiya, Kento Takenaka, Kazuo Ohtsuka, Koichiro Kimura, Ryosuke Watanabe, Tomoyuki Fujioka, Toshimitsu Fujii, Mamoru Watanabe, Ukihide Tateisi
  • Journal Title: Eur J Radiol Volume: 133 Pages: 109362-109362
  • DOI: 10.1016/j.ejrad.2020.109362
  • 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
• [Presentation] Corticosteroid discontinuation and clinical outcomes in patients with moderately to severely active Crohn's disease treated with upadacitinib. (2023)
  • Author(s): M.C. Dubinsky, G. D’Haens, O. Dewit, P. Juillerat, R. Panaccione, T. Fujii, A.P. Lacerda, E. Dubcenco S. Anyanwu, C. Doshi, M. Mallick, A. Garrison, J. Liu, E.V. Loftus Jr.
  • Organizer: 18th Congress of ECCO.
  • Int'l Joint Research
• [Presentation] Selective IgA deficiency induces spontaneous inflammation in the ileum. (2022)
  • Author(s): Nagaishi T, Yamada D, Inoue T, Blumberg RS, Okamoto R, Adachi T.
  • Organizer: The 51st Annual meeting of Japanese Society of Immunology.
  • Int'l Joint Research
• [Presentation] 選択的IgA欠損によって誘発される回腸特異的な免疫異常. (2022)
  • Author(s): 永石宇司, 山田大貴, 渡部太郎, 渡辺守, 岡本隆一, 安達貴弘.
  • Organizer: 第59回 日本消化器免疫学会
• [Presentation] Spontaneous inflammation specifically in the ileum is induced by selective IgA deficiency. (2022)
  • Author(s): Nagaishi T, Yamada D, Adachi T, Watanabe M, Okamoto R, Blumberg RS.
  • Organizer: Annual meeting of American Gastroenterology Association, Digestive Disease Week
  • Int'l Joint Research
• [Presentation] Patients with moderate to severe Crohn’s Disease with and without prior biologic failure demonstrate improved endoscopic outcomes with risankizumab: Results from phase 3 induction and maintenance trials. (2022)
  • Author(s): 10.Ferrante, M.;Cao, Q.;Fujii, T.;Rausch, A.;Neimark, E.;Song, A.;Wallace, K.;Kligys, K.;Zhou, Q.;Kalabic, J.;Feagan, B.G.
  • Organizer: 17th Congress of ECCO
  • Int'l Joint Research
• [Presentation] IMPACT OF INFLAMMATORY BURDEN ON EFFICACY OF UPADACITINIB MAINTENANCE THERAPY IN ULCERATIVE COLITIS: RESULTS FROM THE PHASE 3 U-ACHIEVE STUDY. (2022)
  • Author(s): B. Feagan, J.-F. Colombel, J. Torres, T. Fujii, W. Zhou, X. Yao, Y. Sanchez Gonzalez, D. Ilo, X. Roblin.
  • Organizer: UEGW2022
  • Int'l Joint Research
• [Presentation] Clinical and Endoscopic Improvements with Risankizumab Induction and Maintenance Dosing Versus Placebo are Observed Irrespective of Number of Prior Failed Biologics. (2022)
  • Author(s): Marc Ferrante, Laurent Peyrin-Biroulet, Axel Dignass, David T. Rubin, Silvio Danese, Geert D'Haens, Kristina Kligys, Sofie Berg, Jasmina Kalabic, Javier Zambrano, Yafei Zhang, Toshimitsu Fujii, and Remo Panaccione.
  • Organizer: American College of Gastroenterology Annual Scientific Meeting. 2022
  • Int'l Joint Research
• [Presentation] 生物学的製剤無効歴の有無を問わず中等症から重症のクローン病患者においてリサンキズマブによる内視鏡的評価項目の改善が示された：第3相寛解導入・維持試験の結果. (2022)
  • Author(s): 藤井 俊光, Marc Ferrante, Qian Cao, Astrid Rausch, Ezequiel Neimark, Alexandra Song5, Kori Wallace, Kristina Kligys, Qing Zhou, Jasmina Kalabic, Brian Feagan.
  • Organizer: 日本消化器病学会週間JDDW2022
• [Presentation] Infliximab failure難治性潰瘍性大腸炎の病態の後継治療への影響. (2022)
  • Author(s): 齊藤詠子、藤井俊光、大塚和朗、岡本隆一
  • Organizer: 日本消化器病学会週間JDDW2022
• [Presentation] 潰瘍性大腸炎直腸病変に対する局所製剤治療効果の比較検討. (2022)
  • Author(s): 田中将平, 藤井俊光, 中西裕之, 石堂舜, 稲田賢人, 桐野桜, 山下洸司, 延澤翼, 松本浩明, 早川優香, 掛川達矢, 樋口麻友, 高浦健太, 金子俊, 前屋舗千明, 玉城信治, 安井豊, 土谷薫, 黒崎雅之, 泉並木.
  • Organizer: 日本消化器病学会週間JDDW2022
• [Presentation] 再燃寛解型潰瘍性大腸炎に対する最適な治療法の検討. (2022)
  • Author(s): 前屋舖千明, 玉城信治, 石堂舜, 延澤翼, 松本浩明, 樋口麻友, 高浦健, 田中 将平, 安井豊, 藤井俊光, 土谷薫, 中西裕之, 黒崎雅之, 泉並木.
  • Organizer: 日本消化器病学会週間JDDW2022
• [Presentation] IMID(免疫介在性炎症性疾患)におけるT2Tの共通点 炎症性腸疾患におけるタイトコントロールの重要性について. (2022)
  • Author(s): 藤井俊光
  • Organizer: 第50回日本臨床免疫学会総会.
  • Invited
• [Presentation] 内科と外科でクローン病を診る クローン病診療における小腸病変の重要性とTreat to Target. (2022)
  • Author(s): 藤井俊光
  • Organizer: 第77回日本大腸肛門病学会学術集会.
  • Invited
• [Presentation] 中等症から重症のクローン病患者に対するリサンキズマブ導入療法による内視鏡的寛解/改善 の効果：国際共同第3 相導入療法試験（ADVANCE）. (2022)
  • Author(s): 藤井俊光, 村越かおる, 大野浩太, 久松理一.
  • Organizer: 第108回日本消化器内視鏡学会総会.
• [Presentation] 重症潰瘍性大腸炎に対する内科治療と広域内科外科連携の試み. (2022)
  • Author(s): 藤井俊光、藤原俊、岡本隆一.
  • Organizer: 第59回日本腹部救急医学会総会.
• [Presentation] IBD新規治療の使い分け（anti-TNF以降治験も含め） (2021)
  • Author(s): 藤井俊光
  • Organizer: 2021年度日本炎症性腸疾患学会医師教育セミナー
• [Presentation] クローン病に対するMRenterocolonographyによるTreat to Target -無作為化比較試験 (2021)
  • Author(s): 藤井俊光、桂田武彦、岩本史光、黒崎雅之、矢内常人、酒井義法、山地統、北詰良雄、前屋舗千明、竹中健人、河本亜美、本林麻衣子、日比谷秀爾、清水寛路、齊藤詠子、長堀正和、大塚和朗、泉並木、渡辺守、岡本隆一
  • Organizer: 第12回日本炎症性腸疾患学会
• [Presentation] 潰瘍性大腸炎標準治療とピットフォール (2021)
  • Author(s): 藤井俊光
  • Organizer: 第76回日本大腸肛門病学会学術集会
  • Invited
• [Presentation] 分子標的薬時代の潰瘍性大腸炎治療戦略 (2021)
  • Author(s): 藤井俊光
  • Organizer: JDDW（日本消化器関連学会週間）
  • Int'l Joint Research
• [Presentation] クローン病におけるMRenterocolonographyによるTight Control (2021)
  • Author(s): 藤井俊光、桂田武彦、岩本史光、黒崎雅之、矢内常人、酒井義法、山地統、北詰良雄、前屋舗千明、竹中健人、河本亜美、本林麻衣子、日比谷秀爾、清水寛路、齊藤詠子、長堀正和、大塚和朗、泉並木、渡辺守、岡本隆一
  • Organizer: JDDW（日本消化器関連学会週間）
• [Presentation] クローン病小腸病変モニタリングの重要性 (2021)
  • Author(s): 藤井俊光
  • Organizer: JDDW（日本消化器関連学会週間）
  • Invited
• [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): Takashi 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
• [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