Development of new immunotherapy through the regulation of mitochondrial function

• Project/Area Number: 16K15232
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: University of Fukui
• Principal Investigator: Sugai Manabu 福井大学, 学術研究院医学系部門, 教授 (90303891)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: IgE / IgA / TGF-b / レチノイン酸 / クラススイッチ組換え / 形質細胞分化 / 免疫療法

Outline of Final Research Achievements

Allergic hypersensitivity disorders are characterized by an excessive immunoglobulin E (IgE) response. IgE stimulates basophils and mast cells to release biologically active mediators in an antigen-specific manner. Steroids is commonly used for treatment of allergic disease to dampen inflammatory response. However, steroids also inhibit useful immune reaction. In this study, we tried to develop novel therapeutic approach to improve allergic hypersensitivity through reducing responsible IgE antibody and enhancing protective IgA antibody, whose antigen specificity is the same as IgE.

Academic Significance and Societal Importance of the Research Achievements

アレルギーをおさえるための一つの方法として、ステロイドを用いた免疫抑制がある。しかしこの方法は他の免疫反応も同時に抑制するといった負の側面から逃れられない。他方、アレルギーの根本的治療としての『脱感作療法』は、施術にかなりの熟練を要する。また一時的に治療が成功しても、再度アレルギー状況に陥ることもあり、効果の持続性に問題がある。しかし今回提案する方法は、今までにない発想に基づいた新しい治療法である。この研究で得られた結果は、この新規治療法の実現に必要な知見を提供する。

Research Products

• [Journal Article] Dephosphorylation of protamine 2 at serine 56 is crucial for murine sperm maturation in vivo (2019)
  • Author(s): Itoh Katsuhiko、Kondoh Gen、Miyachi Hitoshi、Sugai Manabu、Kaneko Yoshiyuki、Kitano Satsuki、Watanabe Hitomi、Maeda Ryota、Imura Akihiro、Liu Yu、Ito Chizuru、Itohara Shigeyoshi、Toshimori Kiyotaka、Fujita Jun
  • Journal Title: Science Signaling Volume: 12 Issue: 574 Pages: 7232-7234
  • DOI: 10.1126/scisignal.aao7232
  • Peer Reviewed / Open Access
• [Journal Article] Blocking LC3 lipidation and ATG12 conjugation reactions by ATG7 mutant protein containing C572S (2019)
  • Author(s): Nitta A, Hori K, Tanida I, Igarashi A, Deyama Y, Ueno T, Kominami E, Sugai M, Aoki K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 508(2) Issue: 2 Pages: 521-526
  • DOI: 10.1016/j.bbrc.2018.11.158
  • Peer Reviewed
• [Journal Article] Immune responses against Lewis Y tumor-associated carbohydrate antigen displayed densely on self-assembling nanocarriers (2018)
  • Author(s): Yamazaki Yuji、Nambu Yukiko、Ohmae Masashi、Sugai Manabu、Kimura Shunsaku
  • Journal Title: Organic & Biomolecular Chemistry Volume: 16 Issue: 43 Pages: 8095-8105
  • DOI: 10.1039/c8ob01955j
  • Peer Reviewed
• [Journal Article] Direct evidence for the age-dependent demise of GNAS -mutated cells in oral fibrous dysplasia (2018)
  • Author(s): Isobe Yu、Takahashi Katsu、Kiso Honoka、Nakao Kazumasa、Ikeno Masayuki、Koyama Noriaki、Sugai Manabu、Shimizu Akira、Haga Hironori、Bessho Kazuhisa
  • Journal Title: Archives of Oral Biology Volume: 93 Pages: 133-140
  • DOI: 10.1016/j.archoralbio.2018.05.018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb-/-Runx2+/- Murine Incisors. (2018)
  • Author(s): Saito K, Takahashi K, Huang B, Asahara M, Kiso H, Togo Y, Tsukamoto H, Mishima S, Nagata M, Iida M, Tokita Y, Asai M, Shimizu A, Komori T, Harada H, MacDougall M, Sugai M, Bessho K.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5169-5169
  • DOI: 10.1038/s41598-018-23515-y
  • NAID: 120006545187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Publication Preview Source Id2 Determines Intestinal Identity through Repression of the Foregut Transcription Factor Irx5 (2018)
  • Author(s): Mori, K, Nakamura, H, Kurooka, H, Miyachi, H, Tamada, K, Sugai, M,Takumi, T, Yokota, Y
  • Journal Title: Mol Cell Biol Volume: 38 Issue: 9
  • DOI: 10.1128/mcb.00250-17
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis. (2017)
  • Author(s): Ebina-Shibuya R, Matsumoto M, Kuwahara M, Jang KJ, Sugai M, Ito Y, Funayama R, Nakayama K, Sato Y, Ishii N, Okamura Y, Kinoshita K, Kometani K, Kurosaki T, Muto A, Ichinose M, Yamashita M, Igarashi K.
  • Journal Title: The Journal of biological chemistry Volume: 292 Issue: 44 Pages: 18098-18112
  • DOI: 10.1074/jbc.m117.808535
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tubulointerstitial Nephritis with IgM-Positive Plasma Cells. (2017)
  • Author(s): Takahashi N, Kimura H et al
  • Journal Title: J Am Soc Nephrol. Volume: 28 Issue: 12 Pages: 3688-3698
  • DOI: 10.1681/asn.2016101074
  • Peer Reviewed / Open Access
• [Presentation] Mitochondrial function in cell fate determination of activated B cells (2017)
  • Author(s): Manabu Sugai
  • Organizer: Consortium of Biological Sciences 2017