Molecular mechanisms of Th9 cell-mediated chronic inflammation

• Project/Area Number: 25893033
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: YAGI Ryoji 千葉大学, 医学(系)研究科(研究院), 特任准教授 (20392152)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 免疫学 / アレルギー・ぜんそく / Th9 / ヘルパーT細胞 / 遺伝子発現制御 / サイトカイン / IL-9 / Th9細胞 / アレルギー / 転写因子 / 炎症 / 遷延化 / T細胞 / 免疫

Outline of Final Research Achievements

Naive CD4 T cells can differentiate into several T helper (Th) cell subsets, Th1, Th2, Th17, regulatory T cells and follicular T cells. Recently Th9 cells have been added into Th cell subsets. Th9 cells are known to induce proliferation of mast cells and secretion of mucus from goblet cells and also to be involved in allergic diseases. IL-4 and TGFβ are required for Th9 cell differentiation from naive CD4 T cells in vitro. However, the molecular mechanism of Th9 cell differentiation and the function of Th9 cells in vivo are not understood yet. To study these questions, we focused on a responsible gene which we found previously and we established an in vivo model to investigate role of the gene on Th9 cell differentiation.

Research Products

• [Journal Article] Pathogenic memory type Th2 cells in allergic inflammation (2014)
  • Author(s): Endo, Y., Hirahara, K., Yagi, R., Tumes, D. J., and Nakayama, T.
  • Journal Title: Trends Immunol Volume: 35(2) Issue: 2 Pages: 69-78
  • DOI: 10.1016/j.it.2013.11.003
  • Peer Reviewed
• [Journal Article] The transcription factor GATA3 is critical for the development of all IL-7Rα-expressing innate lymphoid cells. (2014)
  • Author(s): Yagi, R., Zhong, C., Northrup, D. L., Yu, F., Bouladoux, N., Spencer, S., Hu, G., Barron, L., Sharma, S., Nakayama, T., Belkaid, Y., Zhao, K., and Zhu, J.
  • Journal Title: Immunity Volume: 40 Issue: 3 Pages: 378-388
  • DOI: 10.1016/j.immuni.2014.01.012
  • Peer Reviewed
• [Journal Article] Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression. (2013)
  • Author(s): Hosokawa H, Tanaka T, Kato M, Tohyama H, Hanazawa A, Tamaki Y, Hirahara K, Sakikawa I, Morita A, Nagira M, Suzuki Y, Nakayama T.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 110(46) Issue: 46 Pages: 18626-18631
  • DOI: 10.1073/pnas.1311100110
  • Peer Reviewed
• [Presentation] Role of the transcription factor GATA3 in helper T cell and innate lymphoid cell development (2015)
  • Author(s): Yagi, R., Nakayama, T., and Zhu, J.
  • Organizer: Immunology 2015, The American Association of Immunologists, AAI Annual Meeting
  • Place of Presentation: New Orleans (USA)
  • Year and Date: 2015-05-09
  • Invited
• [Presentation] IL-9 production is a transient feature of differentiating Th2 cells in response to TGFβ. (2014)
  • Author(s): Yagi, R., Sarkar, H. M., Soh, T., Nakayama, T., and Zhu, J.
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2014-12-12
• [Presentation] Role of the transcription factor GATA3 in helper T cell and innate lymphoid cell development. (2014)
  • Author(s): Yagi, R.
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2014-12-11
  • Invited
• [Presentation] Roles of Th2 differentiation-related transcription factors, GATA3, STAT5 and Runx3 in Th9 differentiation (2013)
  • Author(s): 八木良二
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ（千葉市）