Epigenetic regulation of the memory T cell response

• Project/Area Number: 15K08522
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: ONODERA Atsushi 千葉大学, 大学院医学研究院, 准教授 (10586598)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免疫記憶 / 発生・分化 / エピジェネティクス / アレルギー・ぜんそく / 発現制御 / 抗原応答

Outline of Final Research Achievements

Formation of immunological memory after infection or vaccination is a phenomenon known for over 200 years; however, the detailed molecular mechanisms still remain unknown. We have focused on memory helper T cells that play a central role in the immunological memory and built a responsome database integrating all omics datasets we obtained with the memory T cells. Detailed analysis also revealed that epigenetic and posttranscriptional regulation of memory T cells are important for their rapid response to the cognate antigens. The epigenetic mechanism involves spatial interplay between Polycomb and Trithorax group proteins whereas the posttranscriptional mechanism involves a specific RNA binding protein. In the future, I would like to apply knowledge acquired through these studies to development of a new vaccination system or novel methods of prevention and treatment of allergic diseases.

Research Products

• [Journal Article] Anti-tumor immunity via the superoxide-eosinophil axis induced by a lipophilic component of Mycobacterium lipomannan (2017)
  • Author(s): Ito Toshihiro、Hirahara Kiyoshi、Onodera Atsushi、Koyama-Nasu Ryo、Yano Ikuya、Nakayama Toshinori
  • Journal Title: Int. Immunol Volume: 29 Issue: 9 Pages: 411-421
  • DOI: 10.1093/intimm/dxx051
  • Peer Reviewed / Open Access
• [Journal Article] Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells (2017)
  • Author(s): Onodera Atsushi、Kiuchi Masahiro、Kokubo Kota、Kato Miki、Ogino Tomohiro、Horiuchi Shu、Kanai Urara、Hirahara Kiyoshi、Nakayama Toshinori
  • Journal Title: J Immunol Volume: 199 Issue: 3 Pages: 1153-1162
  • DOI: 10.4049/jimmunol.1602129
  • Peer Reviewed / Open Access
• [Journal Article] The Transcription Factor T-bet Limits Amplification of Type I IFN Transcriptome and Circuitry in T Helper 1 Cells (2017)
  • Author(s): Iwata Shigeru、Mikami Yohei、Sun Hong-Wei、Brooks Stephen R.、Jankovic Dragana、Hirahara Kiyoshi、Onodera Atsushi、Shih Han-Yu、Kawabe Takeshi、Jiang Kan、Nakayama Toshinori、Sher Alan、O’Shea John J.、Davis Fred P.、Kanno Yuka
  • Journal Title: Immunity Volume: 46 Issue: 6 Pages: 983-991.e4
  • DOI: 10.1016/j.immuni.2017.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenetic regulation of T-helper cell differentiation, memory, and plasticity in allergic asthma (2017)
  • Author(s): Tumes Damon J.、Papadopoulos Magdalene、Endo Yusuke、Onodera Atsushi、Hirahara Kiyoshi、Nakayama Toshinori
  • Journal Title: Immunol. Rev Volume: 278 Issue: 1 Pages: 8-19
  • DOI: 10.1111/imr.12560
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Th2 cells in health and disease. (2016)
  • Author(s): Nakayama T, Hirahara K, Onodera A, Endo Y, Hosokawa H, Shinoda K, Tumes DJ, Okamoto Y.
  • Journal Title: Annu Rev Immunol. Volume: 35 Issue: 1 Pages: 53-84
  • DOI: 10.1146/annurev-immunol-051116-052350
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Myosin light chain 9 and 12 are functional ligands for CD69 that regulate airway inflammation (2016)
  • Author(s): Hayashizaki, K., Kimura, M. Y., Tokoyoda, K., Hosokawa, H., Shinoda, K., Hirahara, K., Ichikawa, T., Onodera, A., Hanazawa, A., Iwamura, C., Kakuta, J., Muramoto, K., Motohashi, S., Tumes, D. J., Iinuma, T., Yamamoto, H., Ikehara, Y., Okamoto, Y., and Nakayama, T.
  • Journal Title: Sci. Immunol. Volume: 1 Issue: 3
  • DOI: 10.1126/sciimmunol.aaf9154
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Asymmetric action of STAT transcription factors drives transcriptional outputs and cytokine specificity. (2015)
  • Author(s): Hirahara, K., Onodera, A., Villario, A. V., Bonelli, M., Sciume, G., Laurence, A., Sun, H. W., Brooks, S. R., Vahedi, G., Shih, H. Y., Gtierrez-Cruz, G., Iwata, S., Suzuki, R., Mikami, Y., Okamoto, Y., Nakayama, T., Holland, S. M., Hunter, C. A., Kanno, Y., and O’Shea, J. J.
  • Journal Title: Immunity Volume: 42 Issue: 5 Pages: 877-889
  • DOI: 10.1016/j.immuni.2015.04.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spatial interplay between Polycomb and Trithorax complexes controls transcriptional activity in T lymphocytes. (2015)
  • Author(s): Onodera, A., Tumes, D. J., Watanabe, Y., Hirahara, K., Kaneda, A., Sugiyama, F., Suzuki, Y., and Nakayama, T.
  • Journal Title: Mol. Cell. Biol. Volume: 35 Issue: 22 Pages: 3841-3853
  • DOI: 10.1128/mcb.00677-15
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ヘルパーT細胞分化とエピジェネティクス (2015)
  • Author(s): 小野寺淳、中山俊憲
  • Journal Title: 炎症と免疫 Volume: 23 Pages: 199-205
• [Presentation] A quantitative method for evaluating binding positions of Trithorax and Polycomb proteins based on correlation function or entropy. (2016)
  • Author(s): Onodera, A., Ogino, T., Kiuchi, M., Kokubo, K., and Nakayama, T.
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-07
• [Presentation] Spatial interplay between Polycomb and Trithorax complexes controls transcriptional activity in T lymphocytes. (2016)
  • Author(s): Onodera, A., Tumes, D.J., Kiuchi, M., Kokubo, K., Watanabe, Y., Hirahara, K., Kaneda, A., Sugiyama, F., Suzuki, Y., and Nakayama, T.
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: MELBOURNE, AUSTRALIA
  • Year and Date: 2016-08-23
  • Int'l Joint Research
• [Presentation] Fine scale positioning of Polycomb and Trithorax complexes controls transcriptional activity in T lymphocytes. (2015)
  • Author(s): Onodera, A., Kiuchi, M., Wada, T., Kanno, T., Hayashizaki, K., and Nakayama, T.
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道・札幌市)
  • Year and Date: 2015-11-18
• [Presentation] ポリコーム／トライソラックス複合体による免疫細胞記憶維持機構の解明 (2015)
  • Author(s): Onodera, A., and Nakayama, T.
  • Organizer: 第25回Kyoto T Cell Conference
  • Place of Presentation: 京都大学芝蘭会館(京都府・京都市)
  • Year and Date: 2015-05-15
• [Presentation] POLYCOMB AND TRITHORAX COMPLEXES CONTROL EPIGENETIC MEMORY OF T HELPER CELLS. (2015)
  • Author(s): Onodera A, Hirahara K and Nakayama T.
  • Organizer: NCI Symposium on Chromosome Biology
  • Place of Presentation: Bethesda, MD, USA
  • Year and Date: 2015-04-16
  • Int'l Joint Research
• [Book] Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects (2018)
  • Author(s): Onodera Atsushi、Kokubo Kota、Nakayama Toshinori
  • Publisher: IntechOpen
  • ISBN: 9789535138556
• [Remarks] 千葉大学大学院医学研究院免疫発生学
  • URL: http://www.m.chiba-u.ac.jp/class/meneki/