Regulation of T cell function by the epigenetic factor Eed

• Project/Area Number: 25460599
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Toho University
• Principal Investigator: NAITO Taku 東邦大学, 医学部, 講師 (10568728)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: エピジェネティクス / Eed / IEL / TGFβ / PRC2 / T細胞分化 / Treg / TCRシグナル伝達

Outline of Final Research Achievements

The role of epigenetic regulation, which establishes and maintains semi-stable gene expression pattern without changes in DNA sequence, in T cell differentiation and function was investigated. When Eed, a gene encoding epigenetic factor involved in histone H3 methylation, was deleted specifically in T cells, proteins associated with a subset of gut IEL (intraepithelial lymphocytes) were highly induced by TGFbeta stimulation in CD4+ T cells. Moreover, the lymphocyte number in gut-affiliated lymphnode increased significantly. These results indicated that epigenetic regulation in T cells is involved in the homeostasis of gut immune system.

Research Products

• [Journal Article] ThPOK represses CXXC5, which induces methylation of histone H3 lysine 9 in Cd40lg promoter by association with SUV39H1: implications in repression of CD40L expression in CD8+ cytotoxic T cells. (2016)
  • Author(s): Tsuchiya Y, Naito T, Tenno M, Maruyama M, Koseki H, Taniuchi I, Naoe Y
  • Journal Title: J Leukoc Biol Volume: 100 Pages: 1-10
  • Peer Reviewed
• [Journal Article] SATB1 Plays a Critical Role in Establishment of Immune Tolerance. (2016)
  • Author(s): Kondo M, Tanaka Y, Kuwabara T, Naito T, Kohwi-Shigematsu T, Watanabe A
  • Journal Title: J Immunol Volume: 196 Issue: 2 Pages: 563-572
  • DOI: 10.4049/jimmunol.1501429
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Epigenetics in T-cell development and function (2014)
  • Author(s): Taku Naito
  • Journal Title: Advances in Neuroimmune Biology Volume: 5 Issue: 3 Pages: 161-170
  • DOI: 10.3233/nib-140090
  • Peer Reviewed
• [Journal Article] Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development. (2014)
  • Author(s): Mishima Y, Wang C, Miyagi S, Saraya A, Hosokawa H, Mochizuki-Kashio M, Nakajima-Takagi Y, Koide S, Negishi M, Sashida G, Naito T, Ishikura T, Onodera A, Nakayama T, Tenen DG, Yamaguchi N, Koseki H, Taniuchi I, Iwama A.
  • Journal Title: Nature Communications Volume: 18 Issue: 1 Pages: 5872-5882
  • DOI: 10.1038/ncomms6872
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptional regulation of the Ikzf1 locus. (2013)
  • Author(s): Yoshida T, Landhuis E, Dose M, Hazan I, Zhang J, Naito T, Jackson AF, Wu J, Perotti EA, Kaufmann C, Gounari F, Morgan BA, Georgopoulos K.
  • Journal Title: Blood Volume: 122 Issue: 18 Pages: 3149-3159
  • DOI: 10.1182/blood-2013-01-474916
  • Peer Reviewed
• [Journal Article] Epigenetic Thpok silencing limits the time window to choose CD4+ helper-lineage fate in the thymus. (2013)
  • Author(s): Hirokazu Tanaka
  • Journal Title: EMBO Journal Volume: 17 Issue: 8 Pages: 1183-94
  • DOI: 10.1038/emboj.2013.47
  • Peer Reviewed
• [Presentation] Eed affects the differentiation of CD8aa+ TCRab+ intraepithelial lymphocytes. (2015)
  • Author(s): Yukihide Matsui, Taku Naito, Yuriko Tanaka, Motonari Kondo
  • Organizer: 第44回日本免疫学会学術集会
  • 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: 2015-11-20
• [Presentation] Nuclear protein SATB1 is required for development of experimental autoimmune encephalomyelitis. (2015)
  • Author(s): Yasushi Akiba, Taku Kuwabara, Yuriko Tanaka, Taku Naito, Motonari Kondo
  • Organizer: 第44回日本免疫学会学術集会
  • 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: 2015-11-19
• [Presentation] Role of Eed in TGFb-induced Th subset differentiation. (2015)
  • Author(s): Taku Naito, Yuriko Tanaka, Ichiro Taniuchi, Motonari Kondo
  • Organizer: 第44回日本免疫学会学術集会
  • 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: 2015-11-19
• [Presentation] Role of Eed in T-cell lineage decision and maintenance (2014)
  • Author(s): Taku Naito, Sawako Muroi, Ichiro Taniuchi, Motonari Kondo
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2014-12-10
• [Presentation] SATB1 is required for development of experimental autoimmune encephalomyelitis (2014)
  • Author(s): Taku Kuwabara, Yasushi Akiba, Yuriko Tanaka, Taku Naito, Motonari Kondo
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2014-12-10
• [Presentation] Role of Eed in T-cell differentiation and function.
  • Author(s): Taku Naito, Sawako Muroi,Motonari Kondo and Ichiro Taniuchi
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 幕張メッセ、千葉