Memory Th1/Th2 cell differentiation and its epigenetic regulation

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390147
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: NAKAYAMA Toshinori 千葉大学, 大学院・医学研究院, 教授 (50237468)
• Project Period (FY): 2009 – 2011
• Keywords: 免疫記憶

Research Abstract

Immunological Memory is a central theme in acquired immunity. The findings from the research on Immunological Memory will contribute to the development of more effective and safer vaccines against infectious diseases, as well as can be beneficial to the development of therapeutic vaccines for controlling so called pathogenic immune memory cells that trigger allergy or autoimmune diseases, and furthermore, to the development of vaccines for cancer. In this study, we found that Polycomb group molecule EZH2 and Trithorax group molecules Men-1 control the generation and functional maintenance of Th2 memory cells.

Research Products

• [Journal Article] Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance (2012)
  • Author(s): Satoh, M., Andoh, Y., Clingan, S. C., Ogura, H., Fujii, S., Nakayama, T., Taniguchi, M., Hirata, N., Ishimori, N., Tsutsui, H., Onoe, K. Iwabuchi, K
  • Journal Title: PLoS ONE Volume: 7(2)
  • DOI: DOI:10.1371/journal.pone.0030568
  • Peer Reviewed
• [Journal Article] MurineSchnurri-2 controls Natural Killer cellfunction and lymphoma development (2012)
  • Author(s): Yamashita, J., Iwamura, C., Mitsumori, K., Hosokawa, H., Sasaki, T., Takahashi, M., anaka, H., Kaneko, K., Hanazawa, A., Watanabe, Y., Shinoda, K., Tumes, D., Motohashi, S. Nakayama, T
  • Journal Title: Leuk.Lymphoma Volume: 53(3) Pages: 479-86
  • DOI: DOI:10.3109/10428194.2011.625099
  • Peer Reviewed
• [Journal Article] The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy (2011)
  • Author(s): Kidoya, H., Kunii, N., Naito, H., Muramatsu, T., Okamoto, Y., Nakayama, T. Takakura, N
  • Journal Title: Oncogene in press
  • DOI: DOI:10.38/onc.2011.489
  • Peer Reviewed
• [Journal Article] Cigarette smoke-induced pulmonary inflammation is attenuated in CD69-deficient mice (2011)
  • Author(s): Tsuyusaki, J., Kuroda, F., Kasuya, Y., Ishizaki, I., Yamauchi, K., Sugimoto, H., Kono, T., Iwamura, C., Nakayama, T. Tatsumi, K
  • Journal Title: J. Recept. Sig. Transduct. Res Volume: 31 Pages: 434-439
  • DOI: DOI:10.3109/10799893.2. 011.631929
  • 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 Pages: 733-745
  • DOI: DOI:10.1016/j.immuni.2011.08.017
  • Peer Reviewed
• [Journal Article] IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation (2011)
  • Author(s): Takahashi, K., Hirose, K., Kawashima, S., Niwa, Y., Wakashin, H., Iwata, A., Tokoyoda, K., Renauland Nakad, J.-C., Iwamoto, I., Nakayama, T. Nakajima, H
  • Journal Title: J. Allergy Ciln. Immunol Volume: 128 Pages: 1067-1076
  • DOI: DOI:10.1016/j.jaci.2011.06.018
  • Peer Reviewed
• [Journal Article] Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin (2011)
  • Author(s): Yamauchi, K., Kasuya, Y., Kuroda, F., Tanaka, K., Tsuyusaki, J., Ishizaki, S., Matsunaga, H., Iwamura, C., Nakayama, T. Tatsumi, K
  • Journal Title: Respir. Res Volume: 12 Pages: 131
  • DOI: DOI:10.1186/1465-9921-12-131
  • Peer Reviewed
• [Journal Article] NKT-cell-based immunotherapies in clinical trials (2011)
  • Author(s): Exley, M. A., N Nakayama, T
  • Journal Title: Clin. Immunol Volume: 140 Pages: 117-118
  • DOI: DOI:10.1016/j.clim.2011.04.015
  • Peer Reviewed
• [Journal Article] Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer (2011)
  • Author(s): Motohashi, S., Okamoto, Y., Yoshino, I. Nakayama, T
  • Journal Title: Ciln. Immunol Volume: 140 Pages: 1647-176
  • DOI: DOI:10.1016/j.clim.2011.01.009
  • Peer Reviewed
• [Journal Article] Memory type 2 helper T cells induce long-lasting anti-tumor immunityby activating natural killer cells (2011)
  • Author(s): Kitajima, M., Ito, T., Tumes, J. D., Endo, Y., Onodera, A., Hashimoto, K., Motohashi, S., Yamashita, M., Nishimura, T., Ziegler, F. S. Nakayama, T
  • Journal Title: Cancer Res Volume: 71 Pages: 4790-4798
  • DOI: DOI:10.1158/0008-5472.CAN-10-1572
  • Peer Reviewed
• [Journal Article] TSLP enhances the function of helper type2 cells. Eur (2011)
  • Author(s): Kitajima, M., Lee, H.-C., Nakayama, T. Ziegler, S. F
  • Journal Title: J. Immunol Volume: 41 Pages: 1862-1870
  • DOI: DOI:10.1002/eji.201041195
  • Peer Reviewed
• [Journal Article] Repressor of GATA negatively regulates murine contact hypersensitivity through the inhibition of type-2 allergic responses (2011)
  • Author(s): Hirasaki, Y., Iwamura, C., Yamashita, M., Ito, T., Kitajima, M., Shinoda, K., Namiki, T., Terasawa, K. Nakayama, T
  • Journal Title: Clin. Immunol Volume: 139 Pages: 267-276
  • DOI: DOI:10.1016/j.clim.2011.02.009
  • 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 Pages: 6378-6389
  • DOI: DOI:10.4049/jimmunol.1100179
  • Peer Reviewed
• [Journal Article] ncrease of regulatory T cells and the ratio of specific IgE to total IgE are candidates for response monitoring or prognostic biomarkers in 2-year sublingual immunotherapy (SLIT) for Japanese cedar pollinosis (2011)
  • Author(s): Fujimura, T., Yonekura, S., Horiguchi, S., Taniguchi, Y., Saito, A., Yasueda, H., Inamine, A., Nakayama, T., Takemori, T., Taniguchi, M., Sakaguchi, M. Okamoto, Y
  • Journal Title: Clin. Immunol Volume: 139 Pages: 65-74
  • DOI: DOI:10.1016/j.clim.2010.12.022
  • Peer Reviewed
• [Journal Article] Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy (2011)
  • Author(s): Yamasaki, K., Horiguchi, S., Kurosaki, M., Kunii, N., Nagato, K., Hanaoka, H., Shimizu, N., Ueno, N., Yamamoto, S., Taniguchi, M., Motohashi, S., Nakayama, T. Okamoto, Y
  • Journal Title: Clin. Immunol Volume: 138 Pages: 255-265
  • DOI: DOI:10.1016/j.clim.2010.11.014 2011
  • Peer Reviewed
• [Journal Article] Apolipoprotein A-II suppressed concanavalin A-induced hepatitis via the inhibition of CD4 T cell function (2011)
  • Author(s): Yamashita, J., Iwamura, C., Sasaki, T., Mitsumori, K., Ohshima, K., Hada, K., Hara, N., Takahashi, M., Kaneshiro, Y., Tanaka, H., Kaneko, K. Nakayama, T
  • Journal Title: J. Immunol Volume: 186 Pages: 3410-3420
  • DOI: DOI:10.4049/jimmunol.1002924
  • Peer Reviewed
• [Journal Article] Migration and immunological reaction after the administration of αGalCer-pulsed antigen -presenting cells into the submucosa of patients with head and neck cancer (2011)
  • Author(s): Kurosaki, M., Horiguchi, S., Yamasaki, K., Uchida, Y., Motohashi, S., Nakayama, T., Sugimoto, A. Okamoto, Y
  • Journal Title: Cancer Immunol Volume: 60 Pages: 207-215
  • DOI: DOI:10.1007/s00262-010-0932-z
  • Peer Reviewed
• [Journal Article] Activation of pulmonary invariant NKT cells leads to exacerbation of acute lung injury caused by LPS through local production of IFN-_γ and TNF-α by Gr-1^+ monocytes (2011)
  • Author(s): Aoyagi, T., Yamamoto, N., Hatta, M., Tanno, D., Miyazato, A., Ishii, K., Suzuki, K., Nakayama, T., Taniguchi, M., Kunishima, H., Hirakata, Y., Kaku, M. Kawakami, K
  • Journal Title: Int. Immunol Volume: 23 Pages: 97-108
  • DOI: DOI:10.1093/intimm/dxq460 2011
  • Peer Reviewed
• [Journal Article] Role of NKT cells in allergic asthma. Curr (2010)
  • Author(s): Iwamura, C. Nakayama, T
  • Journal Title: Opin. Immunol Volume: 22 Pages: 807-81
  • DOI: DOI:10.1016/j.coi.2010.10.008
  • Peer Reviewed
• [Journal Article] STAT6-mediated displacement of polycomb by trithorax complex establishes long-term maintenance of GATA3 expression in T helper type 2 cells (2010)
  • Author(s): Onodera, A., Yamashita, M., Endo, Y., Kuwahara, M., Tofukuji, S., Hosokawa, H., Kanai, A., Suzuki, Y. Nakayama, T
  • Journal Title: J. Exp. Med Volume: 207 Pages: 2493-2506
  • DOI: DOI:10.1084/jem.20100760
  • Peer Reviewed
• [Journal Article] The TCR-mediated signaling pathways that control the direction of helper T cell differentiation (2010)
  • Author(s): Nakayama, T. Yamashita, M
  • Journal Title: Semin. Immunol Volume: 22 Pages: 303-309
  • DOI: DOI:10.1016/j.smim.2010.04.010
  • Peer Reviewed
• [Journal Article] Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species (2010)
  • Author(s): Suzuki, S., Tanaka, T., Poyurovsky, V. M., Nagano, H., Mayama, T., Ohkubo, S., Lokshin, M., Hosokawa, H., Nakayama, T., Suzuki, Y., Sugano, S., Sato, E., Nagao, T., Yokote, K., Tatsuno, I. Prives, C
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 7461-7466
  • DOI: DOI:10.1073/pnas.1002459107
  • Peer Reviewed
• [Journal Article] Polycomb group gene product Ring1B regulates Th2-driven airway inflammation through the inhibition of Bim-mediated apoptosis of effector Th2 cells in the lung (2010)
  • Author(s): Suzuki, A., Iwamura, C., Shinoda, K., Tumes, J. D., Kimura, Y. M., Hosokawa, H., Endo, Y., Horiuchi, S., Tokoyoda, K., Koseki, H., Yamashita, M. Nakayama, T
  • Journal Title: J. Immunol Volume: 184 Pages: 4510-4520
  • DOI: DOI:10.4049/jimmunol.0903426
  • Peer Reviewed
• [Journal Article] The induced regulatory T-cell level, defined as the proportion of IL10+Foxp3+ cells among CD25+CD4+ leukocytes, is an available therapeutic biomarker for sublingual immunotherapy : A preliminary report (2010)
  • Author(s): Fujimura, T., Yonekura, S., Taniguchi, Y., Horiguchi, S., Saito, A., Yasueda, H., Nakayama, T., Takemori, T., Taniguchi, M., Sakaguchi, M. Okamoto, Y
  • Journal Title: Int. Arch. Allergy Immunol Volume: 153 Pages: 378-387
  • DOI: DOI:10.1159/000316349
  • Peer Reviewed
• [Journal Article] lColor-coded real-time cellular imaging of T lymphocyte accumulation and focus formation in mouse asthma model (2010)
  • Author(s): Hasegawa, A., Hayashi, K., Kishimoto, H., Yang, M., Tofukuji, S., Suzuki, K., Nakajima, H., Hoffman, R. M., Shirai, M. Nakayama, T
  • Journal Title: J Allergy Clin. Immunol Volume: 125 Pages: 461-468
  • DOI: DOI:10.1016/j.jaci.2009.09.016
  • Peer Reviewed
• [Journal Article] Organization of immunological memory by bone marrow stroma (2010)
  • Author(s): Tokoyoda, K., Hauser A. E., Nakayama, T. Radbruch, A
  • Journal Title: Nat. Rev. Immunol Volume: 10 Pages: 193-200
  • DOI: DOI:10.1038/nri2727
  • Peer Reviewed
• [Journal Article] Naringenin chalcone suppresses allergic asthma by inhibiting the type-2 function of CD4 T cells (2010)
  • Author(s): Iwamura, C., Shinoda, K., Yoshimura, M., Watanabe, Y., Obata, A. Nakayama, T
  • Journal Title: Allergology International Volume: 59 Pages: 67-73
  • DOI: DOI:10.2332/allergolint.09-OA-0118
  • Peer Reviewed
• [Journal Article] CD69 controls the pathogenesis of allergic airway inflammation (2009)
  • Author(s): Miki, H. T., Hasegawa, A., Iwamura, C., Shinoda, K., Tofukuji, S., Watanabe, Y., Hosokawa, H., Motohashi, S., Hashimoto, K., Shirai, M., Yamashita, M. Nakayama, T
  • Journal Title: J. Immunol Volume: 183 Pages: 8203-8215
  • DOI: DOI:10.4049/jimmunol.0900646
  • Peer Reviewed
• [Journal Article] he Runx3 transcription factor augments Th1 and down-modulates Th2 phenotypes by interacting with and attenuating GATA3 (2009)
  • Author(s): Kohu, K., Ohmori, H., Wong, W. F., Onda, D., Wakoh, T., Kon, S., Yamashita, M., Nakayama, T., Kubo, M. Satake, M
  • Journal Title: J. Immunol Volume: 183 Pages: 7817-7824
  • DOI: DOI:10.4049/jimmunol.0802527
  • Peer Reviewed
• [Journal Article] Enhanced Th2 cell differentiation and allergen-induced airway inflammation in Zfp35-deficient mice (2009)
  • Author(s): Kitajima, M., Iwamura, C., Miki, H. T., Shinoda, K., Endo, Y., Watanabe, Y., Shinnakasu, R., Hosokawa, H., Hashimoto, K., Motohashi, S., Koseki, H., Ohara, O., Yamashita, M. Nakayama, T.
  • Journal Title: J. Immunol Volume: 183 Pages: 5388-5396
  • DOI: DOI:10.4049/jimmunol.0804155
  • Peer Reviewed
• [Journal Article] Combination therapy of in vitro-expanded natural killer T cells and α-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma (2009)
  • Author(s): Kunii, N., Horiguchi, S., Motohashi, S., Yamamoto, H., Ueno, N., Yamamoto, S., Sakurai, D., Taniguchi, M., Nakayama, T. Okamoto, Y
  • Journal Title: Cancer Sci Volume: 100 Pages: 1092-1098
  • DOI: DOI:10.1111/j.1349-7006.2009.01135
  • Peer Reviewed
• [Journal Article] Critical role of the Polycomb and Trithorax complexes in the maintenance of CD4 T cell memory (2009)
  • Author(s): Nakayama, T. Yamashita, M
  • Journal Title: Semin. Immunol Volume: 21 Pages: 78-83
  • DOI: DOI:10.1016/j.smim.2009.02.001
  • Peer Reviewed
• [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. 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] Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3 (2011)
  • Author(s): Onodera, A., Horiuchi, S., Hosokawa, H., Watanabe, Y., Suzuki, Y. Nakayama, T
  • Organizer: NCI Symposium on Chromosome Structure and Function
  • Place of Presentation: Bethesda, MD
  • Year and Date: 2011-11-01
• [Presentation] NKT cell-mediated regulation of antigen-specific memory Th2 cell function (2011)
  • Author(s): Nakayama, T. Iwamura, C
  • Organizer: 6th International Symposium on CD1 and NKT Cells
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-09-25
• [Presentation] Epigenetic regulation of GATA3 expression and its target genes in Th2 cells (2011)
  • Author(s): Nakayama, T
  • Organizer: 45th Joint Working Conference on Immunology and Viral Diseases
  • Place of Presentation: CA, USA
  • Year and Date: 2011-06-20
• [Presentation] Regulation of memory Th2 cell function and allergic airway inflammation via polycomb and trithorax molecules (2011)
  • Author(s): Nakayama, T. Onodera, A
  • Organizer: 30th Congress of the European Academy of Allergy and Clinical Immunology
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2011-06-15
• [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 (2011)
  • Author(s): 堀内周, 小野寺淳, 細川裕之, 渡邊友紀子, 鈴木穣, 中山俊憲
  • Organizer: 第5回日本エピジェネティックス研究会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-19
• [Presentation] Generation and maintenance of memory Th1/Th2 cell identity (2010)
  • Author(s): Endo, Y., Onodera, A. Nakayama, T
  • Organizer: 2010 ASBMB
  • Place of Presentation: Tahoe City, USA
  • Year and Date: 2010-10-02
• [Presentation] STAT6-mediated displacement of Polycomb by Trithorax complex establishes long-term maintenance of GATA3 expression in Th2 cells (2010)
  • Author(s): Onodera, A., Endo, Y. Nakayama, T
  • Organizer: 2010 ASBMB
  • Place of Presentation: Tahoe City, USA
  • Year and Date: 2010-10-01
• [Presentation] CD4 T cell memory controlled by Polycomb and Trithorax molecules (2010)
  • Author(s): Nakayama, T
  • Organizer: The 10th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji, JAPAN
  • Year and Date: 2010-09-10
• [Presentation] 免疫記憶、ポリコ.ムとトライソラックスによる制御 (2010)
  • Author(s): 中山俊憲
  • Organizer: 第4回日本エピジェネティクス研究会
  • Place of Presentation: 米子
  • Year and Date: 2010-05-29
• [Patent(Industrial Property Rights)] 関節リウマチに対する抗IL-6受容体抗体療法の有効性の予測方法 (2011)
  • Inventor(s): 中島裕史(国立大学法人千葉大学大学院), 池田啓(国立大学法人千葉大学大学院), 加々美新一郎( 国立大学法人千葉大学大学院), 鈴木快枝(国立大学法人千葉大学大学院), 中山俊憲(国立大学法人千葉大学大学院), 岩本逸夫, 古田俊介, 小原收(財団法人かずさディー・エヌ・エー研究所), 野中謙, 山下政克(財団法人かずさディー・エヌ・エー研究所), 的場亮
  • Industrial Property Rights Holder: 国立大学法人千葉大学、財団法人かずさディー・エヌ・エー研究所
  • Industrial Property Number: 日本特願、2011-156921
  • Filing Date: 2011-07-14
• [Patent(Industrial Property Rights)] INHIBITION OF CD69 FOR TREATMENT OF INFRAMMATORY CONDITIONS (2010)
  • Inventor(s): 中山俊憲(国立大学法人千葉大学), 長谷川明洋(国立大学法人山口大学), 白井睦訓国立大学法人山口大学)
  • Industrial Property Rights Holder: 国立大学法人千葉大学・国立大学法人山口大学
  • Industrial Property Number: 米国レギュラー出願、US12/945153
  • Filing Date: 2010-11-12
  • Overseas