Development of a novel method to reversibly inactivate gene products by using chemical genetics

• Project/Area Number: 16K15289
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Kurosaki Tomohiro 大阪大学, 免疫学フロンティア研究センター, 特任教授(常勤) (50178125)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ケミカルジェネティクス / 時空間的制御 / Syk / 胚中心 / Cre / syk / 時空間 / 可逆的阻害 / syｋ / 免疫学 / B細胞 / 可逆的変異法 / 低分子阻害剤

Outline of Final Research Achievements

Development of a new method to reversibly inactivate specific genes in a tempo-spatial way is very important for biological research. Here, as a model system, we have tried to reversibly inactivate the Syk tyrosine kinase in the germinal center phase. We have identified the chemical component which inhibits the mutant Syk, but not wildtype Syk. We have also established mice harboring inducible Cre only in the germinal center B cell phase.

Research Products

• [Journal Article] The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help. (2017)
  • Author(s): Inoue T, Shinnakasu R, Ise W, Kawai C, Egawa T, Kurosaki T.
  • Journal Title: J. Exp. Med. Volume: 214 Issue: 4 Pages: 1181-1198
  • DOI: 10.1084/jem.20161263
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A distinct subpopulation of CD25－ T-follicular regulatory cells localizes in the germinal centers (2017)
  • Author(s): James Badger Wing, Yohko Kitagawa, Michela Locci, Hannah Hume, Christopher Tay, Takayoshi Morita, Yujiro Kidani, Kyoko Matsuda, Takeshi Inoue, Tomohiro Kurosaki, Shane Crotty, Cevayir Coban, Naganari Ohkura, and Shimon Sakaguchi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 114 Issue: 31 Pages: 6400-6400
  • DOI: 10.1073/pnas.1705551114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] Stromal interaction molecule 1 haploinsufficiency causes maladaptive response to pressure overload. (2017)
  • Author(s): Ohba T, Watanabe H, Murakami M, Iino K, Adachi T, Baba Y, Kurosaki T, Ono K, Ito H.
  • Journal Title: PLoS One Volume: 12 Issue: 11 Pages: 1-14
  • DOI: 10.1371/journal.pone.0187950
  • Peer Reviewed / Open Access
• [Journal Article] BACH transcription factors in innate and adaptive immunity (2017)
  • Author(s): Igarashi K, Kurosaki T, Roychoudhuri R.
  • Journal Title: Nat. Rev. Immunol. Volume: 印刷中 Issue: 7 Pages: 437-450
  • DOI: 10.1038/nri.2017.26
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of memory B and plasma cell differentiation. (2017)
  • Author(s): Shinnakasu R, Kurosaki T.
  • Journal Title: Curr. Opin. Immunol. Volume: 45 Pages: 126-131
  • DOI: 10.1016/j.coi.2017.03.003
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis. (2016)
  • Author(s): Ohmi Y, Ise W, Harazono A, Takakura D, Fukuyama H, Baba Y, Narazaki M, Shoda H, Takahashi N, Ohkawa Y, Ji S, Sugiyama F, Fujio K, Kumanogoh A, Yamamoto K, Kawasaki N, Kurosaki T, Takahashi Y, Furukawa K.
  • Journal Title: Nature Communications Volume: in press Issue: 1 Pages: 11205-11205
  • DOI: 10.1038/ncomms11205
  • NAID: 120007135549
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Whole-Virion Influenza Vaccine Recalls an Early Burst of High-Affinity Memory B Cell Response through TLR Signaling (2016)
  • Author(s): Taishi Onodera, Akira Hosono, Takato Odagiri, Masato Tashiro, Shuichi Kaminogawa, Yoshinobu Okuno, Tomohiro Kurosaki, Manabu Ato, Kazuo Kobayashi, and Yoshimasa Takahashi
  • Journal Title: Journal of Immunology Volume: 196(10) Issue: 10 Pages: 4172-84
  • DOI: 10.4049/jimmunol.1600046
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulated selection of germinal center cells into the memory B cell compartment. (2016)
  • Author(s): Shinnakasu, R., Inoue, T., Kometani, K., Moriyama, S., Adachi, Y., Nakayama, M., Takahashi, Y., Fukuyama, H., Okada, T.,Kurosaki,T.
  • Journal Title: Nat. Immunol. Volume: 17 Issue: 7 Pages: 861-9
  • DOI: 10.1038/ni.3460
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop. (2016)
  • Author(s): Kuwahara M, Ise W, Ochi M, Suzuki J, Kometani K, Maruyama S, Izumoto M, Matsumoto A, Takemori N, Takemori A, Shinoda K, Nakayama T, Ohara O, Yasukawa M, Sawasaki T, Kurosaki T, Yamashita M.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12596-12596
  • DOI: 10.1038/ncomms12596
  • Peer Reviewed / Open Access
• [Journal Article] Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1 (2016)
  • Author(s): Ishikawa E, Kosako H, Yasuda T, Ohmuraya M, Araki K, Kurosaki T, Saito T, Yamasaki S
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 12756-12756
  • DOI: 10.1038/ncomms12756
  • NAID: 120006535062
  • Peer Reviewed / Open Access
• [Journal Article] Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program. (2016)
  • Author(s): Ikawa T, Masuda K, Endo TA, Endo M, Isono K, Koseki Y, Nakagawa R, Kometani K, Takano J, Agata Y, Katsura Y, Kurosaki T, Vidal M, Koseki H, Kawamoto H.
  • Journal Title: Genes. Dev. Volume: 30 Issue: 22 Pages: 2475-2485
  • DOI: 10.1101/gad.290593.116
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation. (2016)
  • Author(s): Kuroda E, Ozasa K, Temizoz B, Ohata K, Koo CX, Kanuma T, Kusakabe T, Kobari S, Horie M, Morimoto Y, Nakajima S, Kabashima K, Ziegler SF, Iwakura Y, Ise W, Kurosaki T, Nagatake T, Kunisawa J, Takemura N, Uematsu S, Hayashi M, Aoshi T, Kobiyama K, Coban C, Ishii KJ.
  • Journal Title: Immunity. Volume: 45(6) Issue: 6 Pages: 1299-1310
  • DOI: 10.1016/j.immuni.2016.11.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Selection of germinal-center B cells into memory B cell or plasma cell Compartment (2017)
  • Author(s): Kurosaki, T.
  • Organizer: The 6th NIF Winter School on Advanced Immunology
  • Place of Presentation: Singapore
  • Year and Date: 2017-01-22
  • Invited
• [Presentation] 液性免疫オペレーション機構 (2017)
  • Author(s): 黒崎知博
  • Organizer: 免疫サマースクール
  • Invited
• [Presentation] Selection mechanism of germinal center cells into plasma fate (2017)
  • Author(s): Kurosaki, T.
  • Organizer: The 19th Germinal Centre Conference
  • Int'l Joint Research
• [Presentation] Selection of Germinal Center B Cells into the Memory B Cell or Plasma Cell Compartment (2017)
  • Author(s): Kurosaki, T.
  • Organizer: KAI International Meeting 2017
  • Int'l Joint Research / Invited
• [Presentation] 液性免疫記憶オペレーション機構 (2017)
  • Author(s): 黒崎知博
  • Organizer: 2017年度生命科学系学会合同年次大会（ConBio2017）
  • Invited
• [Presentation] Selection mechanisms of germinal center B cells into the memory B cell compartment (2016)
  • Author(s): Shinnakasu, R.
  • Organizer: 45th Annual Meeting of the Japanese Society for Immunology.
  • Place of Presentation: 沖縄コンベンションセンター、沖縄
  • Year and Date: 2016-12-05
  • Invited
• [Presentation] Fate decisions of germinal center B cells into the memory B cell or plasma cell compartment (2016)
  • Author(s): Kurosaki, T.
  • Organizer: 4th Antibody Symposium
  • Place of Presentation: Singapore
  • Year and Date: 2016-11-14
  • Invited
• [Presentation] Fate decisions of germinal center B cells into the memory B cell or plasma cell compartment (2016)
  • Author(s): Kurosaki, T.
  • Organizer: The International Symposium for Advanced Immunology Commemorating the 10th anniversary of IFReC and the 77th anniversary of Prof. Tadamitsu Kishimoto's birth
  • Place of Presentation: Osaka International Convention Center, Osaka, Japan
  • Year and Date: 2016-11-01
  • Int'l Joint Research / Invited
• [Presentation] Overview of germinal center immunity (2016)
  • Author(s): Kurosaki, T.
  • Organizer: The 13th International Workshop on Autoantibodies and Autoimmunity (IWAA2016)
  • Place of Presentation: The Westin Miyako Kyoto, Kyoto, Japan
  • Year and Date: 2016-10-11
  • Int'l Joint Research / Invited
• [Presentation] Memory B cell generation mechanisms (2016)
  • Author(s): Kurosaki, T.
  • Organizer: Annual program of monthly lectures
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2016-09-08
  • Invited
• [Presentation] Transcriptional regulation in memory B cell development (2016)
  • Author(s): Kurosaki, T.
  • Organizer: EMBO conference “Lymphocyte Antigen Receptor Signaling”
  • Place of Presentation: Siena, Italy
  • Year and Date: 2016-09-03
  • Int'l Joint Research / Invited
• [Presentation] Instructive selection of germinal center B cells into the memory compartment (2016)
  • Author(s): Kurosaki, T.
  • Organizer: International congress of Immunology 2016
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research / Invited
• [Presentation] Instructive selection of germinal center B cells into the memory compartment (2016)
  • Author(s): Kurosaki, T.
  • Organizer: Antibody and Fc Receptor Biology: Bench to Bedside A Special Symposium to Honor Jeffrey V. Ravetch on his 65th Birthday
  • Place of Presentation: New York, USA
  • Year and Date: 2016-05-09
  • Int'l Joint Research / Invited
• [Presentation] B細胞を介する自己免疫抑制 (2016)
  • Author(s): 黒崎知博
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2016-04-21
  • Invited
• [Remarks] Laboratory of Lymphocyte Differentiation
  • URL: http://lymph.ifrec.osaka-u.ac.jp/index_j.html