A basic research aimed at realizing the treatment of inflammatory diseases using engineered Treg cells

• Project/Area Number: 16K21751
• Research Category: Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyushu University
• Principal Investigator: Chinen Takatoshi 九州大学, 医学研究院, 講師 (80432912)
• Project Period (FY): 2018 – 2021
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥56,290,000 (Direct Cost: ¥43,300,000、Indirect Cost: ¥12,990,000)
• Keywords: 免疫学 / 制御性T細胞 / 炎症 / 抗原 / 膠原病・アレルギー内科学 / 免疫関連疾患 / 免疫制御

Outline of Final Research Achievements

Regulatory T cells (Treg) function as modulators of immune responses. The basic mechanism of immunosuppression by these cells has not yet been fully elucidated. In this study, we focused on antigenic receptors on regulatory T cells to elucidate the role of these receptors. We also generated genetically engineered regulatory T cells by artificially modifying the receptor and examined whether they could be used for the treatment of inflammatory disorders.

Academic Significance and Societal Importance of the Research Achievements

炎症の行き過ぎに起因する様々な難治性疾患に対する新規治療法の一つとして、制御性T細胞の持つこの抑制能を活用する事が期待されているが、それを実現する為には、この細胞による免疫抑制の基本的な動作メカニズムを詳細に解明する必要がある。本研究では、制御性T細胞上に発現する抗原受容体の役割を解明すべく研究を行った。制御性T細胞を用いた炎症性疾患治療を実現するにあたり不可欠な有用な知見が得られた。

Research Products

• [Int'l Joint Research] メモリアルスローンケタリングキャンサーセンター(米国)
• [Journal Article] Superiority of mucosal incision-assisted biopsy over ultrasound-guided fine needle aspiration biopsy to diagnose small gastric subepithelial lesions : A propencity score matching analysis. (2020)
  • Author(s): Minoda Y, Chinen T, Osoegawa T, Itaba S, Haraguchi K, Akiho H, Aso A, Sumida Y, Komori K, Ogino H, Ihara E, Ogawa Y.
  • Journal Title: BMC gastroenterology Volume: 20 Issue: 1
  • DOI: 10.1186/s12876-020-1170-2
  • Peer Reviewed / Open Access
• [Journal Article] The Efficacy and Safety of a Promising Single-Channel Endoscopic Closure Technique for Endoscopic Treatment-Related Artificial Ulcers : A Pilot Study. (2020)
  • Author(s): Minoda Y, Ihara E, Ogino H, Komori K, Otsuka Y, Ikeda H, Esaki M, Chinen T, Matsuguchi T, Takahashi S, Shiga N, Yoshimura R, Ogawa Y.
  • Journal Title: Gastrointestinal Tumors Volume: 7 Issue: 1-2 Pages: 21-29
  • DOI: 10.1159/000503994
  • Peer Reviewed / Open Access
• [Journal Article] Interleukin-1β as a predictor of glucocorticoid response in ulcerative colitis. (2020)
  • Author(s): Okuno H, Ogino H, Ihara E, Nishioka K, Iboshi Y, Chinen T, Ochiai T, Akiho H, Nakamura K, Gotoda T, Ogawa Y.
  • Journal Title: Digestion Volume: May 20 Issue: 3 Pages: 1-11
  • DOI: 10.1159/000507435
  • Peer Reviewed
• [Journal Article] Efficacy of endoscopic ultrasound with artificial intelligence for the diagnosis of gastrointestinal stromal tumors. (2020)
  • Author(s): Minoda Y, Ihara E, Komori K, Ogino H, Otsuka Y, Chinen T, Tsuda Y, Ando K, Yamamoto H and Ogawa Y.
  • Journal Title: Journal of Gastroenterology Volume: 55 Issue: 12 Pages: 1119-1126
  • DOI: 10.1007/s00535-020-01725-4
  • Peer Reviewed
• [Journal Article] Role of the IL-23-T-bet/GATA3 axis for the pathogenesis of Ulcerative colitis. (2020)
  • Author(s): Ogino H, Fukaura K, Iboshi Y, Nagamatsu Y, Okuno H, Nishioka K, Nishihara Y, Tanaka Y, Chinen T, Ihara E and Ogawa Y.
  • Journal Title: Inflammation Volume: 44 Issue: 2 Pages: 592-603
  • DOI: 10.1007/s10753-020-01358-y
  • Peer Reviewed
• [Journal Article] 消化管における慢性炎症 (2020)
  • Author(s): 荻野 治栄, 田中 義将, 知念 孝敏, 小森 圭司, 伊原 栄吉, 小川 佳宏
  • Journal Title: 消化器クリニカルアップデート Volume: 2 Pages: 24-28
• [Journal Article] 経口免疫寛容の誘導による免疫制御 (2020)
  • Author(s): 知念 孝敏
  • Journal Title: 医学のあゆみ Volume: 275 Issue: 1 Pages: 98-102
• [Journal Article] Clinical characterization of vonoprazan-refractory gastroesophageal reflux disease. (2019)
  • Author(s): Hamada S, Ihara E, Ikeda H, Muta K, Ogino H, Chinen T, Tanaka Y, Ogawa Y
  • Journal Title: Digestion Volume: In press Issue: 2 Pages: 197-204
  • DOI: 10.1159/000503340
  • Peer Reviewed
• [Journal Article] Involvement of different receptor subtypes in prostaglandin e2-induced contraction and relaxation in the lower esophageal sphincter and esophageal body. (2019)
  • Author(s): Bai X, Ihara E, Otsuka Y, Tsuruta S, Hirano K, Tanaka Y, Ogino H, Hirano M, Chinen T, Akiho H, Nakamura K, Oda Y, Ogawa Y
  • Journal Title: Eur J Pharmacol Volume: 857 Pages: 172405-172405
  • DOI: 10.1016/j.ejphar.2019.172405
  • Peer Reviewed
• [Journal Article] Objective validity of the JNET classification system for the differential diagnosis of colorectal polyps. (2019)
  • Author(s): Minoda Y, Ogino H, Chinen T, Ihara E, Haraguchi K, Hirotada A, Takizawa N, Aso A, Tomita Y, Esaki M, Komori K, Otsuka Y, Iwasa T, Ogawa Y.
  • Journal Title: Digestive Endoscopy Volume: 31 Issue: 5 Pages: 544-551
  • DOI: 10.1111/den.13393
  • Peer Reviewed
• [Journal Article] Mucosal profiles of immune molecules related to T helper and regulatory T cells predict future relapse in patients with quiescent ulcerative colitis. (2019)
  • Author(s): Fukaura K, Iboshi Y, Ogino H, Ihara E, Nakamura K, Nishihara Y, Nishioka K, Chinen T, Iwasa T, Aso A, Goto A, Haraguchi K, Akiho H, Harada N, Ogawa Y.
  • Journal Title: Inflammatory bowel disease Volume: 25 Issue: 6 Pages: 1019-1027
  • DOI: 10.1093/ibd/izy395
  • NAID: 40022181938
  • Peer Reviewed
• [Journal Article] Tregによる免疫抑制メカニズム (2019)
  • Author(s): 知念 孝敏
  • Journal Title: 医学のあゆみ(特集 制御性T細胞研究の現在) Volume: 268 Pages: 1091-1100
• [Journal Article] Extrathymically Generated Regulatory T Cells Establish a Niche for Intestinal Border-Dwelling Bacteria and Affect Physiologic Metabolite Balance. (2018)
  • Author(s): Campbell C, Dikiy S, Bhattarai SK, Chinen T, Matheis F, Calafiore M, Hoyos B, Hanash A, Mucida D, Bucci V, Rudensky AY.
  • Journal Title: Immunity Volume: 48 Issue: 6 Pages: 1245-1257
  • DOI: 10.1016/j.immuni.2018.04.013
  • Peer Reviewed / Int'l Joint Research