2018 Fiscal Year Final Research Report
Regulation mechanisms of novel cytokine production by metal trace elements
| Project/Area Number |
16K18518
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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 |
Functional biochemistry
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | サイトカイン / 自然免疫 / RNA結合蛋白質 / 蛋白質輸送 / 転写後制御 |
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| Outline of Final Research Achievements |
The regulation of the proinflammatory cytokine production by immune cells is important for the appropriate inflammatory responses. In this study, we focused on the regulation of cytokine secretion in immune cells. We identified Sortilin which is involved in IFN-α secretion in plasmacytoid dendritic cells (pDC), and Sortilin transcripts degraded posttranscriptionally upon stimulation with various TLR ligands. The nucleotide-binding ability of poly-rC-binding proteins, which can act as a trans-acting factor to stabilize Sortilin mRNA, was impaired by zinc ions and alterations of intracellular zinc affect sortilin expression. Poly-rC-binding proteins may posttranscriptionally regulate Sortilin transcripts by sensing intracellular zinc levels.
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| Free Research Field |
免疫生化学
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| Academic Significance and Societal Importance of the Research Achievements |
免疫細胞から産生される炎症性サイトカインの分泌制御は，適切な炎症応答を保つうえで極めて重要である．本研究では，抗ウイルス免疫に関与する形質細胞様樹状細胞（pDC）において，IFN-α分泌に関わる分子としてSortilinを同定し，その重要性を明らかにした．また，SortilinがTLRシグナル依存的にmRNAレベルで発現制御を受けており，その制御にRNA結合蛋白質であるポリC結合蛋白質が関与している事，更に細胞内の亜鉛がSortilinの制御に関わることを明らかにした．
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