| Project/Area Number |
23590577
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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 |
Immunology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
TAKASHI TANAKA 独立行政法人理化学研究所, 統合生命医科学研究センター, チームリーダー (00415225)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 免疫学 / Th17細胞 / LIM蛋白 / STAT3 / SNP / ユビキチンリガーゼ / 関節リウマチ |
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| Outline of Final Research Achievements |
The differentiation of Th17 cells is tightly regulated, otherwise exaggerated Th17 responses causes autoimmune diseases, including rheumatoid arthritis. We have demonstrated that PDLIM4 bound to STAT3, a key transcription factor for Th17 cell development, and negatively regulated Th17 cell differentiation. PDLIM4 also associated with and recruited to PTPBL, a protein tyrosine phosphatase, through LIM domain, and facilitated dephosphorylation of tyrosine residue of STAT3, thereby suppressing STAT3 signaling. We further found that a single nucleotide polymorphism (SNP) of PDLIM4 is associated with rheumatoid arthritis susceptibility. Interestingly, PDLIM4 mutant containing this amino acid substitution in the LIM domain revealed reduced binding to PTPBL, and therefore partially impaired to dephosphorylate STAT3 and suppress STAT3 signaling. These data delineate an essential role of PDLIM4 to prevent the onset of human autoimmune diseases by negatively Th17 cell differentiation.
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