Analysis of the peripheral T cell function by using IL-7R conditional knockout mice

• Project/Area Number: 24790469
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: TANI-ICHI SHIZUE 京都大学, ウイルス研究所, 助教 (50432331)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: T細胞 / IL-7レセプター / TCR / 免疫学 / サイトカイン / インターロイキン7 / 制御性T細胞

Research Abstract

Little is known about the roles of IL-7 signal in the peripheral T cell function. To address this question, we used peripheral naive T cells from IL-7 receptor (IL-7R) conditional knockout mice or mutant mice of IL-7R-regulatory region and analyzed their TCR responsiveness. We found the possibility that IL-7 signal in naive T cells is required for the proliferation when these T cells are activated by TCR stimulation, and there is positive correlation between IL-7R expression levels on naive T cells and their TCR responsiveness at least in vitro. In addition, we found that regulatory T cells (Tregs) from IL-7R conditional knockout mice show weak suppression activity compared to that of wild-type mice derived Tregs in vitro.

Research Products

• [Journal Article] CD49b-dependent estabhshment of T helper cell memory. (2013)
  • Author(s): Hanazawa, A., Hayashizaki, K.,Shinoda, K., Yagita, H., Okumura, K., Löhning, M., Hara, T., Tani-ichi, S., Ikuta, K., Eckes, B.,Radbruch, A., Tokoyoda, K, and Nakayama, T.
  • Journal Title: Immuno1. Cell Bio1 Volume: 91 Issue: 8 Pages: 524-531
  • DOI: 10.1038/icb.2013.36
  • Peer Reviewed
• [Journal Article] Interleukin-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCRγδ+ intraepithelial lymphocytes. (2013)
  • Author(s): Shitara S, Hara T, Liang B, Wagatsuma K, Zuklys S, Hollander GA, Nakase H, Chiba T, Tani-ichi S, Ikuta K.
  • Journal Title: J Immunol Volume: 190 Issue: 12 Pages: 6173-6179
  • DOI: 10.4049/jimmunol.1202573
  • Peer Reviewed
• [Journal Article] B cell progenitors and precursors change their microenvironment in fetal liver during early development. (2013)
  • Author(s): Tsuneto M, Tokoyoda K, Kajikhina E, Hauser AE, Hara T, Tani-ichi S, Ikuta K, Melchers F.
  • Journal Title: Stem Cells Volume: 31 Issue: 12 Pages: 2800-2812
  • DOI: 10.1002/stem.1421
  • Peer Reviewed
• [Journal Article] Lymphocyte-stromal cell interaction induces IL-7 expression by interferon regulatory factors. (2013)
  • Author(s): Sekai M, Tani-ichi S, Yoneyama M, Fujita T, Kina T, Ikuta K.
  • Journal Title: Mol Immunol Volume: 54 Issue: 3-4 Pages: 378-385
  • DOI: 10.1016/j.molimm.2013.01.002
  • Peer Reviewed
• [Journal Article] Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations. (2013)
  • Author(s): Tani-Ichi, S., Shimba, A., Wagatsuma, K., Miyachi, H., Kitano, S., Imai, K., Hara, T., and Ikuta, K.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 110 Issue: 2 Pages: 612-617
  • DOI: 10.1073/pnas.1219242110
  • NAID: 120005241695
  • Peer Reviewed
• [Journal Article] Role of hepatocyte-derived IL-7 in maintenance of intrahepatic NKT cells and T cells and development of B cells in fetal liver. (2012)
  • Author(s): Liang, B., T. Hara, K. Wagatsuma, J. Zhang, K. Maki, H. Miyachi, S. Kitano, C. Yabe-Nishimura, S. Tani-Ichi, and K. Ikuta
  • Journal Title: Journal of Immunology Volume: 189 Issue: 9 Pages: 4444-4450
  • DOI: 10.4049/jimmunol.1201181
  • Peer Reviewed
• [Journal Article] Identification of IL-7-producing cells in primary and secondary lymphoid organs using IL-7-GFP knock-in mice (2012)
  • Author(s): Hara T, Shitara S, Imai K, Miyachi H, Kitano S, Yao H, Tani-ichi S, Ikuta K
  • Journal Title: J. Immunol Volume: 189(4) Pages: 1577-1584
  • Peer Reviewed
• [Presentation] Role of a TCRγenhancer,Eγ4,in differentiation and function ofγδT cell subsets (2013)
  • Author(s): TANI-ICHI Shizue,WAGATSUMA Keisuke and IKUTA Koichi
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2013-12-11
• [Presentation] Enhancers control locus -wide accessibility of the TCRγlocus in vivo (2012)
  • Author(s): WAGATSUMA Keisuke,TANI-ICHI Shizue and IKUTA Koichi
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] NF-kB and AP-1 signals control IL-7R expression in T cells through CNS (2012)
  • Author(s): TANI-ICHI Shizue and IKUTA Koichi
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] STAT5によるTCR遺伝子再編成の制御機構 (2012)
  • Author(s): 我妻慶祐、谷一靖江、梁涼霧、設楽宗一朗、生田宏一
  • Organizer: 第21回Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2012-07-06
• [Presentation] NFBとAP-1シグナルはCNSを介してIL-7Rの発現レベルを制御する (2012)
  • Author(s): 谷一靖江、生田宏一
  • Organizer: 第21回Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2012-07-06
• [Presentation] Role of a TCRγ enhancer, Eγ4, in differentiation and function of γδ T cell subsets.
  • Author(s): Shizue TANI-ICHI, Keisuke WAGATSUMA, and Koichi IKUTA
  • Organizer: 第42回 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] NFκBとAP-1シグナルはCNSを介してIL-7Rの発現レベルを制御する
  • Author(s): 谷一 靖江、生田 宏一
  • Organizer: 第22回 Kyoto T Cell Conference
  • Place of Presentation: 京都 和順会館
• [Presentation] NF-κB and AP-1 signals control IL-7R expression in T cells through CNS
  • Author(s): Shizue Tani-ichi and Koichi Ikuta
  • Organizer: 第41回 日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場・神戸ポートピアホテル
• [Book] T細胞におけるIL-7レセプターの転写制御と機能Transcriptional regulation and function of IL-7 receptor in T cells :臨床免疫・アレルギー科61(4) (2014)
  • Author(s): 谷一靖江、原崇裕、生田宏一
  • Publisher: 科学評論社
  • URL: http://ci.nii.ac.jp/nrid/9000248200929
• [Remarks]
  • URL: http://www.virus.kyoto-u.ac.jp/about/y2012/ikuta20130124.html
• [Remarks] インターロイキン７レセプターは後期の胸腺細胞亜集団の分化と成熟を制御する
  • URL: http://www.virus.kyoto-u.ac.jp/about/y2012/ikuta20130124.html