ThPOK represses CXXC5, which inhibits CD40L expression in cytotoxic T cells through epigenetic regulation
| Project/Area Number |
25460401
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | National Center for Geriatrics and Gerontology |
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Principal Investigator |
Naoe Yoshinori 国立研究開発法人国立長寿医療研究センター, 運動器疾患研究部, 流動研究員 (50392048)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | ヘルパーT細胞 / 細胞障害性T細胞 / ThPOK / CXXC5 / エピジェネティクス / Ｔ細胞 / T細胞 / Cxxc5 |
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| Outline of Final Research Achievements |
CD40L is induced in helper T cells upon TCR stimulation. However, the mechanisms whereby CD40L becomes expressed in T cells remain unclear. Ｗe showed that CD40L expression in cytotoxic T cells was suppressed by combined epigenetic regulations in the promoter of the Cd40lg gene such as the methylation of CpG dinucleotides, histone H3 lysine 9 (H3K9), H3K27, and H4K20. As ThPOK is critical in helper T cell development, we focused on the role of ThPOK in CD40L expression. CD40L expression is moderately induced by retroviral Thpok transduction into cytotoxic T cells, which was accompanied by a reduction of H3K9 methylation (H3K9me) and H4K20me in the promoter of the Cd40lg gene. ThPOK directly inhibited the expression of CXXC5 that induced H3K9me through an interaction with SUV39H1. In addition to inhibit CD40L induction in activated helper T cells by CXXC5, our findings indicate that CXXC5 was one of the key molecules contributing to repressing CD40L expression in cytotoxic T cells.
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] A novel Cd8-cis-regulatory element preferentially directs expression in CD44hiCD62L+ CD8+ T cells and in CD8αα+ dendritic cells.2015
Author(s)
Sakaguchi S, Hombauer M, Hassan H, Tanaka H, Yasmin N, Naoe Y, Bilic I, Moser MA, Hainberger D, Mayer H, Seiser C, Bergthaler A, Taniuchi I, Ellmeier W.
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Journal Title
J Leukoc Biol.
Volume: 97
Issue: 4
Pages: 635-644
DOI
Related Report
Peer Reviewed
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