Development of a novel method for therapy against autoimmune disease

• Project/Area Number: 15K09520
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Chiba University
• Principal Investigator: Sakamoto Akemi 千葉大学, バイオメディカル研究センター, 准教授 (90359597)
• Co-Investigator(Kenkyū-buntansha): 植松 智 千葉大学, 大学院医学研究院, 教授 (50379088) ; 藤村 理紗 千葉大学, バイオメディカル研究センター, 助教 (30376363) ; 幡野 雅彦 千葉大学, 大学院医学研究院, 教授 (20208523)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自己免疫疾患 / 転写因子 / 阻害剤 / 免疫学 / 内科

Outline of Final Research Achievements

We studied autoimmune disease related factors using animal model in this project. First we developed mouse autoimmune induced models. Among them experimental autoimmune encephalomyelitis (EAE) model represented symptoms.
We found that factor A was critical for development of experimental autoimmune encephalomyelitis because factor A CD4Cre knocked out mice did not show the symptom of the diseases. After searched inhibitors of factor A offered from small chemical library, we finally found several small chemicals as functional inhibitor. These results may useful for development of new therapeutic methods against autoimmune diseases.

Research Products

• [Journal Article] IκBNS enhances follicular helper T-cell differentiation and function downstream of ASCl2. (2017)
  • Author(s): Hosokawa J, Suzuki K, Meguro K, Tanaka S, Maezawa Y, Suto A, Fujimura L, Sakamoto A, Clevers H, Ohara O, Nakajima H
  • Journal Title: J Allergy Clin Immunol. Volume: 140 Pages: 288-291
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Systemic and Local Cytokine Profile in Biliary Atresia. (2017)
  • Author(s): Saito T, Sakamoto A, Hatano M, Iwai J, Higashimoto Y, Yoshida H.
  • Journal Title: Eur J Pediatr Surg Volume: 27 Pages: 280-287
  • Peer Reviewed / Open Access
• [Journal Article] Blocking Liver Autophagy Accelerates Apoptosis and Mitochondrial Injury in Hepatocytes and Reduces Time to Mortality in a Murine Sepsis Model. (2017)
  • Author(s): Oami T, Watanabe E, Hatano M, Teratake Y, Fujimura L, Sakamoto A, Ito C, Toshimori K, Swanson PE, Oda S.
  • Journal Title: Shock. Volume: - Issue: 4 Pages: 427-434
  • DOI: 10.1097/shk.0000000000001040
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of Noninvasive In Vivo Approach to Assess Vascular Permeability in Inflammation Using Fluorescence Imaging. (2017)
  • Author(s): Shimazui T, Nakada TA, Fujimura L, Sakamoto A, Hatano M, Oda S.
  • Journal Title: Shock. Volume: - Issue: 6 Pages: 1-1
  • DOI: 10.1097/shk.0000000000001075
  • Peer Reviewed / Open Access
• [Journal Article] Development of chronic allergic responses by dampening Bcl6-mediated suppressor activity in memory T helper 2 cells. (2017)
  • Author(s): Ogasawara T, Hatano M, Satake H, Ikari J, Taniguchi T, Tsuruoka N, Watanabe-Takano H, Fujimura L, Sakamoto A, Hirata H, Sugiyama K, Fukushima Y, Nakae S, Matsumoto K, Saito H, Fukuda T, Kurasawa K, Tatsumi K, Tokuhisa T, Arima M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114 Issue: 5
  • DOI: 10.1073/pnas.1613528114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptional repression of p27 is essential for murine embryonic development. (2016)
  • Author(s): Teratake Y, Kuga C, Hasegawa Y, Sato Y, Kitahashi M, Fujimura L, Watanabe-Takano H, Sakamoto A, Arima M, Tokuhisa T, Hatano M.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 26244-26244
  • DOI: 10.1038/srep26244
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Suppression of T Cell Autophagy Results in Decreased Viability and Function of T Cells Through Accelerated Apoptosis in a Murine Sepsis Model. (2016)
  • Author(s): Oami T, Watanabe E, Hatano M, Sunahara S, Fujimura L, Sakamoto A, Ito C, Toshimori K, Oda S.
  • Journal Title: Crit Care Med. Volume: Sep 9
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Systemic and local cytokine profile in biliary atresia. (2016)
  • Author(s): Saito T, Sakamoto A, Hatano M, Iwai J, Higashimoto Y, Yoshida H.
  • Journal Title: Eur J Pediatr Surg Volume: ー Issue: 03 Pages: 280-287
  • DOI: 10.1055/s-0036-1592136
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Succinate and lactate production from Euglena gracilis during dark, anaerobic conditions (2016)
  • Author(s): Yuko Tomita, Kazumasa Yoshioka, Hiroko Iijima, Ayaka Nakashima, Osamu Iwata, Kengo Suzuki, Tomohisa Hasunuma, Akihiko Kondo, Masami Yokota Hirai, Takashi Osanai
  • Journal Title: Frontiers in Microbiology Volume: 7 Pages: 2050-2050
  • DOI: 10.3389/fmicb.2016.02050
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Roles of B Cell Leukemia/Lymphoma 3 in the development of T follicular helper cells and the pathogenesis of rheumatoid arthritis. (2015)
  • Author(s): Meguro, K., Suzuki, K., Hosokawa, J., Sanayama, Y., Tanaka, S., Furuta, S., Ikeda, K., Takatori, H, Suto, A., Sakamoto, A., Ohara, O., Nakajima, H.
  • Journal Title: Arthritis & Rheumatology Volume: 67 Issue: 10 Pages: 2651-60
  • DOI: 10.1002/art.39266
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Noninvasive technique using fluorescence imaging to assess vascular permeability in sepsis. (2018)
  • Author(s): Takashi Shimazui, Taka-aki Nakada, Lisa Fujimura, Akemi Sakamoto, Masahiko Hatano, Shigeto Oda
  • Organizer: ISICEM
  • Int'l Joint Research
• [Presentation] Roles of enteric neurons in gut mucosal immunity. (2017)
  • Author(s): Lisa Fujimura, Akemi Sakamoto, Masahiko Hatano
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] 腸管神経細胞分化におけるNcxの機能解析 (2016)
  • Author(s): 小林茉優、幡野雅彦、坂本明美、藤村理紗、寺竹洋一、深谷小百合
  • 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] ２．腸管神経過多マウスを用いた朝刊神経系と免疫系の相互作用の解析 (2016)
  • Author(s): 藤村理紗、坂本明美、幡野雅彦
  • 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] Nczf欠損における個体発生異常とp27との関与 (2015)
  • Author(s): 寺竹洋一、藤村理紗、坂本明美、有馬雅史、幡野雅彦
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 1.Role of enteric neurons in regulation of intestinal homeostasis. (2015)
  • Author(s): Fujimura L. Sakamoto A. Arima M. Tokuhisa T. Hatano M.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-11-18
• [Remarks] 千葉大学バイオメディカル研究センター
  • URL: http://www.m.chiba-u.ac.jp/dept/biomed/
• [Remarks] 千葉大学大学院医学研究院・疾患生命医学
  • URL: http://www.m.chiba-u.ac.jp/dept/biomed/