Challenge to development of innovative method to control monocyte/macrophage lineages

• Project/Area Number: 15K15386
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Morio Tomohiro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30239628)
• Research Collaborator: OTSU Makoto 東京大学医科学研究所, 幹細胞プロセシング分野, 准教授
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 小児免疫 / アレルギー / 膠原病学

Outline of Final Research Achievements

We established a method to differentiate hematopoietic stem cells into monocytes using peripheral blood mononuclear cell derived iPS cells. We further refined a method to induce differentiation of monocytes to dendritic cells and also attempted to induce monocytes into M1 macrophages or to M2 macrophages. In this study, we have identified a novel responsible gene, OAS1, for B/Mo/DC deficiency with alveolar proteinosis through whole exome analysis of affected individuals. iPS cells were established from the patient; and a capacity of the cells to differentiate to monocytes or to DC was examined. In parallel, we generated OAS1 knock in mice to delve into the mechanism of monocyte differentiation defect. Finally, we were successful in inducing Aspergillus fumigatus-specific and Candida albicans-specific T cells using known overlapping peptides and optimized cytokines.

Research Products

• [Journal Article] Abnormal hematopoiesis and autoimmunity in human subjects with germline IKZF1 mutations. (2017)
  • Author(s): Hoshino A, Okada S, Yoshida K, Nishida N, Okuno Y, Ueno H, Yamashita M, Okano T, Tsumura M, Nishimura S, Sakata S, Kobayashi M, Nakamura H, Kamizono J, Mitsui-Sekinaka K, Ichimura T, Ohga S, Nakazawa Y, Takagi M, Imai K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Kojima S, Nonoyama S, Morio T, Kanegane H.
  • Journal Title: J Allergy Clin Immunol. Volume: - Issue: 1 Pages: 390-400
  • DOI: 10.1016/j.jaci.2016.09.029
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hematopoietic Stem Cell Transplantation for XIAP Deficiency in Japan. (2017)
  • Author(s): 3.Ono S, Okano T, Hoshino A, Yanagimachi M, Hamamoto K, Nakazawa Y, Imamura T, Onuma M, Niizuma H, Sasahara Y, Tsujimoto H, Wada T, Kunisaki R, Takagi M, Imai K, Morio T, Kanegane H.
  • Journal Title: J Clin Immunol. Volume: 37 Issue: 1 Pages: 85-91
  • DOI: 10.1007/s10875-016-0348-4
  • Peer Reviewed / Open Access
• [Journal Article] iPS細胞による原発性免疫不全症の治療戦略 (2016)
  • Author(s): 森尾友宏
  • Journal Title: 炎症と免疫 Volume: 24 Pages: 86-90
  • Peer Reviewed
• [Journal Article] 血友病等血液・免疫疾患 原発性免疫不全症 (2016)
  • Author(s): 2．金兼弘和, 森尾友宏
  • Journal Title: 小児科臨床 Volume: 69 Pages: 715-721
• [Presentation] 原発性免疫不全症 (2016)
  • Author(s): 森尾友宏
  • Organizer: 第44回日本臨床免疫学会総会（ビギナーズセミナー）
  • Place of Presentation: 東京都新宿区（京王プラザホテル ）
  • Year and Date: 2016-09-08
• [Presentation] 膠原病・リウマチ性疾患と間違えやすい原発性免疫不全症 (2016)
  • Author(s): 森尾友宏
  • Organizer: 第60回日本リウマチ学会総会学術集会（教育研修講演）
  • Place of Presentation: 神奈川県横浜市西区（パシフィコ横浜）
  • Year and Date: 2016-04-23
• [Presentation] 細胞治療-これからの日本の戦略と課題Strategy for implementation of cell therapy and challenges that lie ahead (2016)
  • Author(s): 森尾友宏
  • Organizer: 第38回日本造血細胞移植学会（シンポジウム）
  • Place of Presentation: 名古屋（名古屋国際会議場）
  • Year and Date: 2016-03-05
• [Presentation] 原発性免疫不全症の遺伝子解析：その成果と限界 (2015)
  • Author(s): 森尾友宏
  • Organizer: 第43回日本臨床免疫学会（ワークショップ）
  • Place of Presentation: 神戸（神戸国際会議場）
  • Year and Date: 2015-10-23
• [Presentation] 稀少性免疫難病の診断と治療 (2015)
  • Author(s): 森尾友宏
  • Organizer: 日本人類遺伝学会第60回大会（特別講演）
  • Place of Presentation: 東京（京王プラザホテル）
  • Year and Date: 2015-10-15
  • Invited
• [Book] リンパ学（リンパ浮腫など特徴的所見を伴う免疫不全症） (2016)
  • Author(s): 森尾友宏（分担執筆）
  • Publisher: 日本リンパ学会事務局
• [Book] リウマチ科（原発性免疫不全症 ） (2015)
  • Author(s): 岡野翼, 森尾友宏（分担執筆）
  • Publisher: 科学評論社
• [Book] 内科（天性免疫不全症候群） (2015)
  • Author(s): 森尾友宏（分担執筆）
  • Publisher: 南江堂
• [Book] 医学のあゆみ（多パラメータ解析による免疫担当細胞亜群同定と機能解析） (2015)
  • Author(s): 森尾友宏, 高島健浩, 今井耕輔（分担執筆）
  • Publisher: 医歯薬出版株式会社