The regulation of memory B cell by DNA demethylation
Project/Area Number |
16K08738
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Kyushu University (2018) Tokyo University of Science (2017) Osaka University (2016) |
Principal Investigator |
TANAKA SHINYA 九州大学, 生体防御医学研究所, 助教 (80462703)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | DNA methylation / Ten-Eleven Translocation / B cells / DNA demethylation / Self tolerance / Ten-Eleven translocation / B細胞分化 / B細胞ホメオスターシス / B細胞自己寛容 / 能動的DNA脱メチル化 |
Outline of Final Research Achievements |
DNA methylation is an well-known epigenetic modification to regulate differentiation and function of multiple linage cells. However, it has been unknown that how the modification regulates the B cell biology. In the current study, we demonstrated that a DNA demethylase, Ten-Eleven Translocation (Tet) prevented autoimmune disease by suppressing aberrant activation of B cells. In contrast, Tet molecules played a pivotal role in differentiation and/or maintenance of effector B cells such as plasma cells, germinal center B cells and memory B cells for appropriate humoral immune response. These data suggest that Tet molecules play a pleiotropic roles in differentiation and/or function of peripheral B cells.
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Academic Significance and Societal Importance of the Research Achievements |
B細胞は、抗体産生を担い生体防御に寄与する免疫細胞であるが、その制御が適切になされない場合は、自己免疫疾患の発症に寄与することが知られている。本研究によって、DNAメチル化制御因子であるTet分子が、B細胞の不適切な過剰活性化を抑制することにより、自己免疫疾患の発症を防ぐ役割を担っていることが明らかとなった。Tet分子活性の人為的操作によって、B細胞が原因となる自己免疫疾患のみならず、ウィルス、バクテリア感染時のB細胞の活性を制御することで液性免疫応答を調節するための新たな標的としての可能性が示唆された。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Trim33 mediates the proinflammatory function of Th17 cells.2018
Author(s)
Tanaka S, Jiang Y, Martinez GJ, Tanaka K, Yan X, Kurosaki T, Kaartinen V, Feng XH, Tian Q, Wang X, Dong C
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Journal Title
Journal of Experimental Medicine
Volume: 215
Pages: 1853-1868
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-32018
Author(s)
Tanaka K, Martinez GJ, Yan X, Long W, Ichiyama K, Chi X, Kim BS, Reynolds JM, Chung Y, Tanaka S, Liao L, Nakanishi Y, Yoshimura A, Zheng P, Wang X, Tian Q, Xu J, O'Malley BW, Dong C
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Journal Title
Cell reports
Volume: 23
Pages: 2318-2329
Related Report
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