Functions of posttranscriptional regulation of GATA3 in Th2 cells

• Project/Area Number: 23790522
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: HOSOKAWA Hiroyuki 千葉大学, 大学院・医学研究院, 助教 (60431756)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アレルギー・ぜんそく / 発現制御 / Th2細胞 / GATA3 / 翻訳後修飾 / アレルギー･ぜんそく

Research Abstract

GATA3 controls differentiation of naive CD4 T cells into Th2 cells. However, the molecular mechanisms how GATA3 induces Th2 cell differentiation remain unclear. In this study, we found that GATA3 is phosphorylated and methylated in the zinc finger domains. Interestingly, the phosphorylated GATA3 could not repress Th1 cell differentiation and the activation of Il5 gene was selectively impaired in methylated GATA3. These results suggest that the regulation of posttranscriptional modifications of GATA3 may lead to the discovery of novel therapeutic targets for the treatment of allergic diseases with less side effects.

Research Products

• [Journal Article] The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-・ and suppresses TH2 differentiation (2012)
  • Author(s): Kuwahara, M., Yamashita, M., Shinoda, K., Tofukuji, S., Onodera, A., Shinnakasu, R., Motohashi, S., Hosokawa, H., Tumes, D., Iwamura, C., Lefebvre, V., and Nakayama, T.
  • Journal Title: Nat. Immunol Volume: 13(8) Issue: 8 Pages: 778-786
  • DOI: 10.1038/ni.2362
  • Peer Reviewed
• [Journal Article] Bmi1 facilitates primitive endoderm formation by stabilizing Gata6 during early mouse development. (2012)
  • Author(s): Lavial, F., Bessonnard, S., Ohnishi, Y., Tsumura, A., Chandrashekran, A., Fenwick, M., Tomaz, R. A., Hosokawa, H., Nakayama, T., Chambers, I., Hiiragi, T., Chazaud, C., and Azuara, V.
  • Journal Title: Genes Dev. Volume: 26 Issue: 13 Pages: 1445-1458
  • DOI: 10.1101/gad.188193.112
  • Peer Reviewed
• [Journal Article] Type II membrane protein CD69 regulates the formation of resting T-helper memory (2012)
  • Author(s): Shinoda, K., Tokoyoda, K., Hanazawa, A., Hayashizaki, K., Zehentmeier, S., Hosokawa, H., Iwamura, C, Koseki, H., Tumes, D.J., Radbruch, A., Nakayama T.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: (in press) Issue: 19 Pages: 7409-7414
  • DOI: 10.1073/pnas.1118539109
  • Peer Reviewed
• [Journal Article] Sublingual administration of Lactobacillus paracasei KW3110 inhibits Th2-dependent allergic responses via upregulation of PD-L2 on dendritic cells. (2012)
  • Author(s): Inamine, A., Sakurai, D., Horiguchi, S., Yonekura, S., Hanazawa, T., Hosokawa, H., Matuura-Suzuki, A., Nakayama, T., and Okamoto, Y.
  • Journal Title: Clin. Immunol. Volume: 143 Issue: 2 Pages: 170-179
  • DOI: 10.1016/j.clim.2012.01.008
  • Peer Reviewed
• [Journal Article] Murine Schnurri-2 controls Natural Killer cell function and lymphoma development (2012)
  • Author(s): Yamashita, J., Iwamura, C., Mitsumori, K., Hosokawa, H., Sasaki, T., Takahashi, M., Tanaka, H., Kaneko, K., Hanazawa, A., Watanabe, Y., Shinoda, K., Tumes, D., Motohashi, S., Nakayama, T.
  • Journal Title: Leuk.Lymphoma Volume: 53 Issue: 3 Pages: 479-486
  • DOI: 10.3109/10428194.2011.625099
  • Peer Reviewed
• [Journal Article] Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3 (2011)
  • Author(s): Endo, Y., Iwamura, C., Kuwahara, M., Suzuki, A., Sugaya, K., Tumes, J. D., Tokoyoda, K. Hosokawa, H., Yamashita, M. Nakayama, T
  • Journal Title: Immunity Volume: 35 Issue: 5 Pages: 733-745
  • DOI: 10.1016/j.immuni.2011.08.017
  • Peer Reviewed
• [Journal Article] Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3 (2011)
  • Author(s): Horiuchi, S., Onodera, A., Hosokawa, H., Watanabe, Y., Tanaka, T., Sugano, S., SuzukiY. Nakayama, T
  • Journal Title: J. Immunol Volume: 186 Issue: 11 Pages: 6378-6389
  • DOI: 10.4049/jimmunol.1100179
  • Peer Reviewed
• [Presentation] Epigenetic regulation of helper T cells by Polycomb and Trithorax complexes (2013)
  • Author(s): Onodera, A., Horiuchi, S., Sasaki, T., Hosokawa, H., Watanabe, Y., Suzuki, Y., and Nakayama, T.
  • Organizer: International Symposium on Genome Science
  • Place of Presentation: Tokyo
  • Year and Date: 2013-01-09
• [Presentation] CD69 regulates the formationof resting T-helper memory (2012)
  • Author(s): Shinoda, K., Tokoyoda, K., Hanazawa, A., Hayashizaki, K., Hosokawa, H., Iwamura, C., Koseki, H., Tumes, D., Radbruch, A., 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] Genome-wide gene expression profiling revealed a critical role for GATA3 inthe maintenance of the Th2 cell phenotype (2012)
  • Author(s): Sasaki, T., Onodera, A., Hosokawa, H., Watanabe, Y., Horiuchi, S., Yamashita, J., 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: 2012-12-05
• [Presentation] 中山俊憲GATA3/Ruvbl2複合体によるCdkn2c(p18,Ink4c)の転写制御を介したTh2細胞増殖制御メカニズムの解析 (2012)
  • Author(s): 細川裕之、田中知明、加藤美紀、遠山裕之、鈴木茜
  • Organizer: 第22回Kyoto T cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2012-07-07
• [Presentation] 肺炎球菌の血流感染及び肺炎における、IL-13による宿主防御の役割/Protective role of IL-13 in sepsis and respiratory infection against S. pneumoniae (2011)
  • Author(s): Yamamoto, N., DelaCruz, C., Takahashi, M., Fujita, T., Hosokawa, H., Nakayama, T., Akahori, Y., Yamamoto, H., Kawakami, K.,Askenase, W. P., and Kanemitsu, K.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-29
• [Presentation] マウス Schnurri-2 は NK細胞の機能とリンパ腫の発症を制御する/Murine Schnurri-2 controls Natural Killer cell function and lymphoma development (2011)
  • Author(s): Yamashita, J., Iwamura, C., Hosokawa, H., Sasaki, T., Tumes, D., Motohashi, S., and Nakayama, T.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-28
• [Presentation] STAT6によって誘導されるポリコ-ムとトライソラックスの置換反応/STAT6-mediated displacement of Polycomb by Trithorax complex establishes long-term maintenance of GATA3 expression in Th2 cells (2011)
  • Author(s): Onodera, A., Yamashita, M., Endo, Y., Kuwahara, M., Tofukuji, S., Hosokawa, H., Horiuchi, S., Watanabe, Y., and Nakayama, T.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-27
• [Presentation] Eomesodermin controls IL-5 production in memory Th2 cells through the inhibition of GATA3 activity. (2011)
  • Author(s): 遠藤裕介、小野寺淳、細川裕之、中山俊憲
  • Organizer: 第21回Kyoto T Cell Conference
  • Place of Presentation: 京都
• [Presentation] GATA3 ChIP-sequence解析を用いたTh2特異的遺伝子の転写調節機構の解明/ Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3. (2011)
  • Author(s): 堀内周、小野寺淳、細川裕之、渡邊友紀子、中山俊憲
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] STAT6によって誘導されるポリコ－ムとトライソラックスのー置換反応/ STAT6-mediated displacement of Polycomb by Trithorax complex establishes long-term maintenance of GATA3 expression in Th2 cells. (2011)
  • Author(s): Onodera, A., Yamashita, M., Endo, Y., Kuwahara, M., Tofukuji, S., Hosokawa, H., Horiuchi, S., Watanabe, Y., and Nakayama, T.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] マウスSchnurri-2はNK細胞の機能とリンパ腫の発症を制御する/ Murine Schnurri-2 controls Natural Killer cell function and lymphoma development. (2011)
  • Author(s): Yamashita, J., Iwamura, C., Hosokawa, H., Sasaki, T., Tumes, D., Motohashi, S., and Nakayama, T.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] 肺炎球菌の血流感染及び肺炎における、IL-13による宿主防御の役割/ Protective role of IL-13 in sepsis and respiratory infection against S. pneumoniae. (2011)
  • Author(s): Yamamoto, N., DelaCruz, C., Takahashi, M., Fujita, T., Hosokawa, H., Nakayama, T., Akahori, Y., Yamamoto, H., Kawakami, K., Askenase, W. P., and Kanemitsu, K
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] GATA3/Ruvbl2複合体によるCdkn2c (p18, Ink4c)の転写制御を介したTh2細胞増殖制御メカニズムの解析
  • Author(s): 細川裕之、田中知明、加藤美紀、遠山裕之、鈴木茜、中山俊憲
  • Organizer: Kyoto T cell Conference
  • Place of Presentation: 京都
• [Presentation] Genome-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell phenotype.
  • Author(s): Sasaki, T., Onodera, A., Hosokawa, H., Watanabe, Y., Horiuchi, S., Yamashita, J., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] CD69 regulates the formation of resting T-helper memory.
  • Author(s): Shinoda, K., Tokoyoda, K., Hanazawa, A., Hayashizaki, K., Hosokawa, H., Iwamura, C., Koseki, H., Tumes, D., Radbruch, A., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Epigenetic regulation of helper T cells by Polycomb and Trithorax complexes.
  • Author(s): Onodera A., Horiuchi S., Sasaki T., Hosokawa H., Watanabe Y., Suzuki Y., Nakayama T.
  • Organizer: International Symposium on Genome Science
  • Place of Presentation: 東京