The regulation of memory Th2 cell-dependent allergic airway inflammation through the IL-33-T1/ST2 pathway.

• Project/Area Number: 24790461
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: ENDO Yusuke 千葉大学, 医学(系)研究科(研究院), 特任講師 (80612192)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アレルギー性気道炎症 / メモリーTh2細胞 / インターロイキン5（IL-5） / IL-33 / Eomesodermin（Eomes） / インターロイキン5(IL-5) / Eomesodermin

Research Abstract

We analyzed the effect of IL-33 on the function of memory Th2 cells. We detected IL-5 production was enhanced by culturing memory Th2 cells with IL-33. IL-33-induced IL-5 augmentation was not observed in T1/ST2-deficient memory Th2 cells. We further demonstrated the involvement of the IL-33-T1/ST2 pathway using memory Th2 cell-dependent airway inflammation models. A significant decrease in the number of inflammatory cells in the BAL fluid was observed in the T1/ST2 KO or IL-33 KO groups as compared to the WT group. We analyzed memory Th2 cells from patients with chronic rhinosinusitis and similar results were obtained to mice memory Th2 cells. These results strongly indicate that IL-33-T1/ST2-IL-5 signal could be a potential therapeutic target for treatment of chronic allergic inflammation induced by memory Th2 cells.

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 polycomb protein Ezh2 regulates differentiation and plasticity of CD4+ T helper type-1 and type-2 cells. (2013)
  • Author(s): Tumes, D. J., Onodera, A., Suzuki, A., Shinoda, K., Endo, Y., Iwamura, C., Hosokawa, H., Koseki, H., Tokoyoda, K., Suzuki, Y., Motohashi, S., and Nakayama, T.
  • Journal Title: Immunity Volume: 39 Issue: 5 Pages: 819-32
  • DOI: 10.1016/j.immuni.2013.09.012
  • Peer Reviewed
• [Journal Article] 免疫記憶の制御 (2013)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 臨床免疫・アレルギ−科 Volume: 60(3) Pages: 309-316
  • NAID: 40019808031
• [Journal Article] Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity. (2013)
  • Author(s): Hosokawa H
  • Journal Title: Proc Natl Acad Sci U SA Volume: - Issue: 12 Pages: 4691-4696
  • DOI: 10.1073/pnas.1220865110
  • Peer Reviewed
• [Journal Article] 免疫記憶の制御 (2013)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 臨床免疫・アレルギ－科 Volume: 60 Pages: 309-316
  • NAID: 40019808031
• [Journal Article] T細胞免疫記憶—メモリ−T細胞の多様性と病因となる細胞集団— (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 臨床免疫・アレルギ−科 Volume: 58(5) Pages: 613-620
  • NAID: 40019493231
• [Journal Article] 記憶CD4 T細胞によるウイルス感染防御、アレルギ−の臨床特集 (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: ウイルス感染と免疫・アレルギ− Volume: 436(32) Pages: 23-27
• [Journal Article] Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo. 109(42) : 16992-16997 (2012). (2012)
  • Author(s): Iwamura, C., Shinoda, K., Endo, Y., Watanabe, Y., Tumes, J. D., Motohashi, S., Kawahara, K., Kinjo, Y., and Nakayama, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109 Issue: 42 Pages: 16992-16997
  • DOI: 10.1073/pnas.1203494109
  • Peer Reviewed
• [Journal Article] Pathogenicメモリ−Th2細胞の同定とIL-5産生分子メカニズムの解明 (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 医学のあゆみ Volume: 242(3) Pages: 266-267
• [Journal Article] IL-5産生pathogenicメモリ−Th2細胞による慢性アレルギ−炎症の制御 (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 実験医学別刷 Volume: 30(6) Pages: 899-904
• [Journal Article] IL-5産生pathogenicメモリーTh2相棒による慢性アレルギー炎症の制御 (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 実験医学別刷 Volume: 6 Pages: 899-904
• [Journal Article] PathogenicメモリーTh2細胞の同定とIL-5産生分子メカニズムの解明 (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 医学のあゆみ Volume: 3 Pages: 266-267
• [Journal Article] 記憶CD4 T細胞によるウィルス感染防御 (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: アレルギーの臨床 Volume: 32 Pages: 23-27
• [Journal Article] T細胞免疫記憶-メモリーT細胞の多様性と病因となる細胞集団- (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Journal Title: 臨床免疫・アレルギー科 Volume: 5 Pages: 613-620
  • NAID: 40019493231
• [Presentation] Functionally distinct Gata3/Chd4 complexes coordinately establish Th2 cell identity (2013)
  • Author(s): Hosokawa, H., Tamaki, Y., Endo, Y., Tumes, D. J., Angela. M., Sarkar, M. H., and Nakayama, T.
  • Organizer: 第42回日本免疫学会総会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2013-12-11
• [Presentation] Generation and maintenance of pathogenic memory CD4 T cells (2013)
  • Author(s): Nakayama, T., Endo, Y., Onodera, A., and Tumes, D. J.
  • Organizer: The 3rd CSI/JSI/KAI Joint Symposium on Immunology
  • Place of Presentation: Korea
  • Year and Date: 2013-12-02
• [Presentation] Pathogenic memory Th2 cells in the airway and regulation by activated NKT cells in vivo (2013)
  • Author(s): Nakayama, T., Iwamura, C., Shinoda, K., and Endo, Y.
  • Organizer: 第63回日本アレルギ−学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-30
• [Presentation] The histone methyltransferase Ezh2 regulates differentiation and plasticity of CD4 T helper cells (2013)
  • Author(s): Tumes, D., Onodera, A., Suzuki, A., Shinoda, K., Endo, Y., Iwamura, C., Hosokawa, H., Koseki, H., Tokoyoda, K., Suzuki, Y., and Nakayama, T.
  • Organizer: AAI Annual Meeting
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2013-05-06
• [Presentation] Regulation of memory CD4 T cell pool size and function by NKT cells in vivo (2012)
  • Author(s): Iwamura, C., Endo, Y., Onodera, A., Watanabe, Y., Suzuki, A., Kinjo, Y., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-06
• [Presentation] Generation and maintenance of memory CD4 T cells (2012)
  • Author(s): Nakayama, T., Endo, Y., Kuwahara, M., Yamashita, M., Iwamura, C., Shinoda, K., and Tokoyoda, K.
  • Organizer: THE 34th NAITO CONFERENCE ON Infection, Immunity, and their control for Health
  • Place of Presentation: Sapporo
  • Year and Date: 2012-10-18
• [Presentation] The histone methyltransferase Ezh2 regulates differentiation and plasticity of CD4 T helper cells.
  • Author(s): Tumes, D., Onodera, A., Suzuki, A., Shinoda, K., Endo, Y., Iwamura, C., Hosokawa, H., Koseki, H., Tokoyoda, K., Suzuki, Y., and Nakayama, T.
  • Organizer: AAI Annual Meeting
  • Place of Presentation: Honolulu, USA
• [Presentation] Pathogenic memory Th2 cells in the airway and regulation by activated NKT cells in vivo.
  • Author(s): Nakayama, T., Iwamura, C., Shinoda, K., and Endo, Y.
  • Organizer: 第63回日本アレルギ－学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] Generation and maintenance of pathogenic memory CD4 T cells.
  • Author(s): Nakayama, T., Endo, Y., Onodera, A., and Tumes, D. J.
  • Organizer: The 3rd CSI/JSI/KAI Joint Symposium on Immunology
  • Place of Presentation: Korea
• [Presentation] Functionally distinct Gata3/Chd4 complexes coordinately establish Th2 cell identity.
  • Author(s): Hosokawa, H., Tamaki, Y., Endo, Y., Tumes, D. J., Angela. M., Sarkar, M. H., and Nakayama, T.
  • Organizer: 第42回日本免疫学会総会学術集会
  • Place of Presentation: 幕張
• [Presentation] Regulation of memory CD4 T cell pool size and function by NKT cells in vivo.
  • Author(s): Iwamura, C., Endo, Y., Onodera, A., Watanabe, Y., Suzuki, A., Kinjo, Y., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Generation and maintenance of memory CD4 T cells.
  • Author(s): Nakayama, T., Endo, Y., Kuwahara, M., Yamashita, M., Iwamura, C., Shinoda, K., and Tokoyoda, K.
  • Organizer: THE 34th NAITO CONFERENCE ON infection, Immunity, and their control for Health.
  • Place of Presentation: 札幌
• [Book] T細胞の免疫記憶、免疫学Update—分子病態の解明と治療への展開— (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Publisher: 南山堂
• [Book] 免疫学Update-分子病態の解明と治療への展開- (2012)
  • Author(s): 遠藤裕介、中山俊憲
  • Publisher: 南山堂