Chromatin dynamics in the regulation of TCR Valpha14Jalpha18 rearrangement

• Project/Area Number: 15K08291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kojo Satoshi 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (70360542)
• Co-Investigator(Renkei-kenkyūsha): TANIGUCHI Masaru 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 特別顧問/グループディレクター (80110310) ; IKAWA Tomokatsu 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (60450392)
• Research Collaborator: OZAWA Ritsuko 国立研究開発法人理化学研究所, 統合生命医科学研究センター, テクニカルスタッフ
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); 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: NKT細胞 / T細胞受容体遺伝子再構成 / クロマチン / 転写因子 / T細胞受容体Vα14Jα18 / NKT細胞特異的転写因子 / クロマチン制御

Outline of Final Research Achievements

NKT cell expresses invariant T cell receptor (TCR) Vα14Jα18 gene and recognizes glycolipid antigen presented on MHC class I-like antigen presenting molecule CD1d. In this study, to clarify the mechanisms of specific gene rearrangement of TCR Vα14Jα18, we tried to find responsible transcription factor(s) by the detection of TCR Vα14 promoter binding proteins. After the screening of candidate genes, which can bind to promoter region of TCR Vα14, 18 gene knockout mouse lines were generated by the CRISPR/Cas9 system. Severe reduction of NKT cell in the thymus and peripheral lymphoid organs was observed in the two knockout lines, suggesting that these Vα14 promoter-binding proteins are important for the regulation of NKT cell development.

Research Products

• [Journal Article] Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors (2018)
  • Author(s): Tenno Mari、Kojo Satoshi、Lawir Divine-Fondzenyuy、Hess Isabell、Shiroguchi Katsuyuki、Ebihara Takashi、Endo Takaho A.、Muroi Sawako、Satoh Rumi、Kawamoto Hiroshi、Boehm Thomas、Taniuchi Ichiro
  • Journal Title: J. Exp. Med Volume: 215 Issue: 2 Pages: 595-610
  • DOI: 10.1084/jem.20171221
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes. (2017)
  • Author(s): Kojo S, Tanaka H, Endo TA, Muroi S, Liu Y, Seo W, Tenno M, Kakugawa K, Naoe Y, Nair K, Moro K, Katsuragi Y, Kanai A, Inaba T, Egawa T, Venkatesh B, Minoda A, Kominami R, Taniuchi I.
  • Journal Title: Nat Commun. Volume: 8 Issue: 1 Pages: 702-702
  • DOI: 10.1038/s41467-017-00768-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Essential Roles of SATB1 in Specifying T Lymphocyte Subsets (2017)
  • Author(s): Kakugawa Kiyokazu、Kojo Satoshi、Tanaka Hirokazu、Seo Wooseok、Endo Takaho A.、Kitagawa Yohko、Muroi Sawako、Tenno Mari、Yasmin Nighat、Kohwi Yoshinori、Sakaguchi Shimon、Kowhi-Shigematsu Terumi、Taniuchi Ichiro
  • Journal Title: Cell Rep Volume: 19 Issue: 6 Pages: 1176-1188
  • DOI: 10.1016/j.celrep.2017.04.038
  • NAID: 40021496454
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alternative pathway for the development of V(α)14(+) NKT cells directly from CD4(-)CD8(-) thymocytes that bypasses the CD4(+)CD8(+) stage. (2017)
  • Author(s): Dashtsoodol N, Shigeura T, Aihara M, Ozawa R, Kojo S, Harada M, Endo TA, Watanabe T, Ohara O, Taniguchi M.
  • Journal Title: Nat Immunol Volume: 18 Issue: 3 Pages: 274-282
  • DOI: 10.1038/ni.3668
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Essential roles of SATB1 in specifying T lymphocyte subsets. (2017)
  • Author(s): 1. Kakugawa K, Kojo S, Tanaka H, Seo W, Endo TA, Kitagawa Y, Muroi S, Tenno M, Yasmin N, Kohwi Y, Sakaguchi S, Kowhi-Shigematsu T, Taniuchi I.
  • Journal Title: Cell Reports Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cell. (2016)
  • Author(s): Kanda M, Yamanaka H, Kojo S, Usui Y, Honda H, Sotomaru Y, Harada M, Taniguchi M, Suzuki N, Atsumi T, Wada H, Baghdadi M, Seino K.
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A Volume: in press
  • NAID: 120005895271
  • Peer Reviewed
• [Journal Article] Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire. (2016)
  • Author(s): Dashtsoodol N, Shigeura T, Ozawa R, Harada M, Kojo S, Watanabe T, Koseki H, Nakayama M, Ohara O, Taniguchi M.
  • Journal Title: PLoS ONE Volume: 11 Issue: 4 Pages: 1-10
  • DOI: 10.1371/journal.pone.0153347
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] α-MSH stimulation contributes to TGF-β1 production via MC1R-MITF signaling pathway in melanoma cell. (2015)
  • Author(s): Hayashi E, Hachiya K, Kojo S, Baghdadi M, Takeuchi S, Yamanaka H, Abe H, Wada H, Seino K.
  • Journal Title: Inflamm.Regen. Volume: 35 Pages: 244-254
  • NAID: 130005114587
  • Peer Reviewed
• [Journal Article] Discovery of NKT cells and development of NKT cell-targeted anti-tumor immunotherapy (2015)
  • Author(s): Taniguchi M, Harada M, Dashtsoodol N, Kojo S.
  • Journal Title: Proceedings of the Japan Academy, Series B Volume: 91 Issue: 7 Pages: 292-304
  • DOI: 10.2183/pjab.91.292
  • NAID: 130005088948
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed / Open Access
• [Presentation] Helper-lineage dominant activity of maturation enhancer in the Cd4 gene is controlled by a silencer-independent and Runx-dependent mechanism. (2017)
  • Author(s): Kojo S, Yasmin N, Tenno M, Muroi S, Taniuchi I.
  • Organizer: 7th International Workshop of Kyoto T cell Conference
  • Place of Presentation: 京大芝蘭会館（京都府京都市）
  • Year and Date: 2017-03-13
  • Int'l Joint Research
• [Presentation] Helper-lineage dominant activity of maturation enhancer in the Cd4 gene is controlled by a silencer-independent and Runx-dependent mechanism. (2017)
  • Author(s): Kojo, S., Yasmin, N., Tenno, M., Muroi, S., Taniuchi, I.
  • Organizer: 7th International Workshop of Kyoto T cell Conference
  • Int'l Joint Research
• [Presentation] Regulation of Runx3 activity in immune system development by the C-terminal end amino acid sequence (2017)
  • Author(s): Kojo, S. Ebihara, T., Ohno-Oishi, M., Muroi, S., Taniuchi, I.
  • Organizer: 第46回日本免疫学会総会・学術集会
• [Presentation] Helper-lineage dominant activity of maturation enhancer in the Cd4 gene is controlled by a silencer-independent and Runx-dependent mechanism. (2016)
  • Author(s): Kojo S, Tenno M, Muroi S, Taniuchi I.
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Microenvironments for immune system Cbfb2 splicing variant confers thymic-homing property in pre-thymic progenitors (2016)
  • Author(s): Tenno M, Muroi S, Kojo S, Naoe Y, Taniuchi I.
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Basic helix-loop-helix transcription factor family, member e40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells (2016)
  • Author(s): Kanda M, Yamanaka H, Kojo S, Harada M, Taniguchi M, Atsumi T, Wada H, Baghdadi M, Seino K.
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Specific requirement of C-terminal Zn finger motifs in Bcl11b transcription factor for lineage dissection upon receiving positive selection signals in the thymus. (2016)
  • Author(s): Kojo S, Seo W, Muroi S, Taniuchi I.
  • Organizer: 16th International Congress of Immunology.
  • Place of Presentation: Melbourne （Australia）
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] 転写因子Bcl11b C末端配列によるT細胞系列決定制御機構. (2016)
  • Author(s): 香城 諭, Seo Wooseok, 室井佐和子, 谷内一郎
  • Organizer: 第26回Kyoto T Cell Conference.
  • Place of Presentation: 延暦寺会館（滋賀県大津市）
  • Year and Date: 2016-05-21
• [Presentation] Roles of Bcl11b transcription factor in the control of CD4/CD8 lineage choice. (2015)
  • Author(s): Satoshi Kojo, Wooseok Seo, Sawako Muroi, Ichiro Taniuchi
  • Organizer: The 44th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Sapporo Convention Center, Sapporo, Japan
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] A validation of the requirement for Vα14 NKT cells for tumor rejection using newly generated Traj18-deficient mice with undisturbed T cell receptor repertoire. (2015)
  • Author(s): Nyambayar Dashtsoodol, Satoshi Kojo 他
  • Organizer: CD1-MR1-2015
  • Place of Presentation: Mantra, Lorne, Australia
  • Year and Date: 2015-11-17
  • Int'l Joint Research
• [Presentation] Alternative developmental pathway of a Vα14+ NKT cell subset bypassing CD4+CD8+ double positive stage. (2015)
  • Author(s): Masaru Taniguchi, Satoshi Kojo 他
  • Organizer: CD1-MR1-2015
  • Place of Presentation: Mantra, Lorne, Australia
  • Year and Date: 2015-11-16
  • Int'l Joint Research