Elucidation of the genetic regulation of novel intestinal intraepithelial lymphocytes with anti-inflammatory properties

• Project/Area Number: 17H05082
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: SUJINO Tomohisa 慶應義塾大学, 医学部(信濃町), 講師 (40464862)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000); Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2018: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 炎症性腸疾患 / 腸管上皮内Ｔ細胞 / 腸管上皮内ＣD4Ｔ細胞 / 内科 / 免疫学

Outline of Final Research Achievements

We found that immune cells in the intestinal epithelium contain suppressor T cells, CD4CD8aaT cells in particular. We have also shown that CD4CD8aa T cells differentiate in part from Treg cells, but the factors that are important for their differentiation are unknown. We identified the key genes to develop CD4CD8aa T cells in intraepithelial compartment. In addition, we showed that the same gene is involved in CD4CD8aaT cells in human patients with inflammatory bowel disease.

Academic Significance and Societal Importance of the Research Achievements

これまで腸管上皮におけるCD4 T細胞については研究が少なかった。マウスモデルにおいてはCD4CD8aa T細胞という腸管上皮内にしか存在しないユニークな細胞集団が腸管上皮のホメオスタシス維持に重要であることが示されており、炎症抑制に同細胞を誘導することが重要であるとされる。しかしこれまで分化に必要な因子、メカニズムは不明であった。そこで、今回同細胞を誘導するのに重要な因子を見つけることで、今後の炎症性腸疾患治療の可能性が期待される。

Research Products

• [Journal Article] Various Endoscopic Features in Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (2021)
  • Author(s): Aoki Yasuhiro、Sujino Tomohisa、Takabayashi Kaoru、Mutakuchi Makoto、Emoto Katsura、Hosoe Naoki、Ogata Haruhiko、Kanai Takanori
  • Journal Title: Case Reports in Gastroenterology Volume: 1 Issue: 1 Pages: 312-322
  • DOI: 10.1159/000513902
  • Peer Reviewed / Open Access
• [Journal Article] Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program (2021)
  • Author(s): London Mariya、Bilate Angelina M.、Castro Tiago B. R.、Sujino Tomohisa、Mucida Daniel
  • Journal Title: Nature Immunology Volume: 22 Issue: 4 Pages: 449-459
  • DOI: 10.1038/s41590-021-00883-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significance of endoscopic deep small bowel evaluation using balloon-assisted enteroscopy for Crohn's disease in clinical remission (2021)
  • Author(s): Takabayashi K, Hosoe N, Kato M, Hayashi Y, Nanki K, Fukuhara K, Mikami Y, Mizuno S, Sujino T, Mutaguchi M, Naganuma M, Yahagi N, Ogata H, Kanai T.
  • Journal Title: J Gastroenterol. Volume: 56(1) Issue: 1 Pages: 25-33
  • DOI: 10.1007/s12328-020-01261-x
  • Peer Reviewed
• [Journal Article] Characteristics of the Mucosal Surface on Scanning Electron Microscopy in Patients with Remitting Ulcerative Colitis (2021)
  • Author(s): Nomura E, Sujino T, Hosoe N, Yoshimatsu Y, Tanemoto S, Takabayashi K, Mutaguchi M, Shimoda M, Naganuma M, Ogata H, Kanai T.
  • Journal Title: Dig Dis Sci. Volume: - Issue: 9 Pages: 1-6
  • DOI: 10.1007/s10620-020-06609-4
  • Peer Reviewed / Open Access
• [Journal Article] Clinical, Endoscopic, and Pathological Characteristics of Immune Checkpoint Inhibitor-Induced Gastroenterocolitis (2021)
  • Author(s): Hayashi Y, Hosoe N, Takabayashi K, Limpias Kamiya KJL, Tsugaru K, Shimozaki K, Hirata K, Fukuhara K, Fukuhara S, Mutaguchi M, Sujino T, Sukawa Y, Hamamoto Y, Naganuma M, Takaishi H, Shimoda M, Ogata H, Kanai T.
  • Journal Title: Dig Dis Sci. Volume: - Issue: 6 Pages: 1-6
  • DOI: 10.1007/s10620-020-06441-w
  • Peer Reviewed
• [Journal Article] Current status of colon capsule endoscopy. (2021)
  • Author(s): Hosoe N, Limpias Kamiya KJL, Hayashi Y, Sujino T, Ogata H, Kanai T.
  • Journal Title: Dig Endosc Volume: 33(4) Issue: 4 Pages: 529-537
  • DOI: 10.1111/den.13769
  • Peer Reviewed
• [Journal Article] Clinical and Endoscopic Characteristics of Pyogenic Granuloma in the Small Intestine: A Case Series with Literature Review (2020)
  • Author(s): Hayashi Yukie、Hosoe Naoki、Takabayashi Kaoru、Kamiya Kenji JL Limpias、Mutaguchi Makoto、Miyanaga Ryoichi、Hirata Kenro、Fukuhara Seiichiro、Mikami Yohei、Sujino Tomohisa、Masugi Yohei、Naganuma Makoto、Ogata Haruhiko、Kanai Takanori
  • Journal Title: Internal Medicine Volume: 59 Issue: 4 Pages: 501-505
  • DOI: 10.2169/internalmedicine.3745-19
  • NAID: 130007798397
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-02-15
  • Peer Reviewed / Open Access
• [Journal Article] Significance of endoscopic deep small bowel evaluation using balloon-assisted enteroscopy for Crohn’s disease in clinical remission (2020)
  • Author(s): Takabayashi Kaoru、Hosoe Naoki、Kato Motohiko、Hayashi Yukie、Nanki Kosaku、Fukuhara Kayoko、Mikami Yohei、Mizuno Shinta、Sujino Tomohisa、Mutaguchi Makoto、Naganuma Makoto、Yahagi Naohisa、Ogata Haruhiko、Kanai Takanori
  • Journal Title: Journal of Gastroenterology Volume: 56 Issue: 1 Pages: 25-33
  • DOI: 10.1007/s00535-020-01737-0
  • Peer Reviewed / Open Access
• [Journal Article] The liver-brain-gut neural arc maintains the Treg cell niche in the gut (2020)
  • Author(s): Teratani T, Mikami Y, Nakamoto N, Suzuki T, Harada Y, Okabayashi K, Hagihara Y, Taniki N, Kohno K, Sibata S, Miyamoto K, Ishigame H, Chu Po-Sung, Sujino T, Suda W, Hattori M, Matsui M, Okada T, Okano H, Inoue M, Yada T, Kitagawa Y, Yoshimura A, Tanida M, Tsuda M, Iwasaki Y, Kanai T.
  • Journal Title: Nature Volume: 585 Issue: 7826 Pages: 591-596
  • DOI: 10.1038/s41586-020-2425-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mucosal concentrations of N-acetyl-5-aminosalicylic acid is related to endoscopic activity in ulcerative colitis patients with mesalamine. (2020)
  • Author(s): Fukuda T, Naganuma M, Takabayashi K, Hagihara Y, Tanemoto S, Nomura E, Yoshimatsu Y, Sugimoto S, Nanki K, Mizuno S, Mikami Y, Fukuhara K, Sujino T, Mutaguchi M, Inoue N, Ogata H, Iwao Y, Abe T, Kanai T.
  • Journal Title: J Gastroenterol Hepatol. Volume: 35 Issue: 11 Pages: 1878-1885
  • DOI: 10.1111/jgh.15059
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of Novel Ultrathin Single-Balloon Enteroscopy for Crohn's Disease: A Propensity Score-Matched Study (2019)
  • Author(s): Takabayashi Kaoru、Hosoe Naoki、Kato Motohiko、Hayashi Yukie、Miyanaga Ryoichi、Nanki Kosaku、Fukuhara Kayoko、Mikami Yohei、Mizuno Shinta、Sujino Tomohisa、Mutaguchi Makoto、Naganuma Makoto、Yahagi Naohisa、Ogata Haruhiko、Kanai Takanori
  • Journal Title: Gut and Liver Volume: - Issue: 5 Pages: 1-6
  • DOI: 10.5009/gnl19228
  • Peer Reviewed / Open Access
• [Journal Article] Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis (2019)
  • Author(s): Yoshimatsu Yusuke、Naganuma Makoto、Sugimoto Shinya、Tanemoto Shun、Umeda Satoko、Fukuda Tomohiro、Nomura Ena、Yoshida Kosuke、Ono Keiko、Mutaguchi Makoto、Nanki Kosaku、Mizuno Shinta、Mikami Yohei、Fukuhara Kayoko、Sujino Tomohisa、Takabayashi Kaoru、Ogata Haruhiko、Iwao Yasushi、Kanai Takanori
  • Journal Title: Digestion Volume: 1 Issue: 4 Pages: 1-7
  • DOI: 10.1159/000501152
  • Peer Reviewed / Open Access
• [Journal Article] Toll-Like Receptor 7 Agonist-Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells. (2018)
  • Author(s): Kiyohara H, Sujino T, Teratani T, Miyamoto K, Arai MM, Nomura E, Harada Y, Aoki R, Koda Y, Mikami Y, Mizuno S, Naganuma M, Hisamatsu T, Kanai T.
  • Journal Title: Cell Mol Gastroenterol Hepatol. Volume: 7 Issue: 1 Pages: 135-156
  • DOI: 10.1016/j.jcmgh.2018.09.010
  • Peer Reviewed / Open Access
• [Journal Article] Steroid-refractory extensive enteritis complicated by ulcerative colitis successfully treated with adalimumab (2017)
  • Author(s): Okabayashi Shinji、Kobayashi Taku、Sujino Tomohisa、Ozaki Ryo、Umeda Satoko、Toyonaga Takahiko、Saito Eiko、Nakano Masaru、Tablante Maria Carla、Morinaga Shojiroh、Hibi Toshifumi
  • Journal Title: intestinal research Volume: 15 Issue: 4 Pages: 535-535
  • DOI: 10.5217/ir.2017.15.4.535
  • Peer Reviewed / Open Access
• [Journal Article] Intestinal immune response is regulated by gut microbe (2017)
  • Author(s): TANEMOTO Shun、SUJINO Tomohisa、KANAI Takanori
  • Journal Title: Japanese Journal of Clinical Immunology Volume: 40 Issue: 6 Pages: 408-415
  • DOI: 10.2177/jsci.40.408
  • NAID: 130006319639
  • ISSN: 0911-4300, 1349-7413
• [Presentation] skin inflammation induce gut inflammation by altering host microbe and immune system (2018)
  • Author(s): 筋野智久
  • Organizer: 免疫学会 2019