| Project/Area Number |
16K19601
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Okayama University |
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Principal Investigator |
MIYAWAKI Yoshia 岡山大学, 医歯薬学総合研究科, 非常勤研究員 (10761116)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | SLE / Ctse / Kaiso / Epigenetics / DNA methylation / CD4陽性T細胞 / CTSE (カテプシンE) / IL10 / 免疫学 / カテプシンE |
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| Outline of Final Research Achievements |
Global DNA hypomethylation in T cells in systemic lupus erythematosus (SLE) patients was involved in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and the transcript level was upregulated in MRL compared with B6. Among them, we focused on a mCGCG which was hypomethylated and mutated to CGGG in MRL. The binding of Kaiso, a repressive transcriptional factor recognized mCGmCG motif was reduced in MRL and EL4 cells treated with 5-azaC and/or Trichostatin A. In addition, IL-10 secretion was reduced in EL4 cells transfected with siCtse. In conclusion, reduced recruitment of Kaiso to the hypometylated mCGCG motif induced the overexpression of Ctse and IL-10 in CD4+ cells which may be involved in the pathogenesis of SLE.
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