| 研究課題/領域番号 |
21K07066
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分49070:免疫学関連
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| 研究機関 | 金沢大学 |
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研究代表者 |
D NYAMBAYAR 金沢大学, 医学系, 准教授 (50443057)
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| 研究分担者 |
渡会 浩志 金沢大学, 医学系, 教授 (70415339)
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| 研究期間 (年度) |
2021-04-01 – 2024-03-31
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| 研究課題ステータス |
中途終了 (2021年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2023年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2022年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2021年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
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| キーワード | invariant NKT / thymus / development / function / differentiation / CD1d / natural killer T / transcription factor |
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| 研究開始時の研究の概要 |
The recent advances in the iNKT cell research field has uncovered many important features of iNKT cell development and function. However, the mechanisms driving the differentiation of iNKT cell functional subsets remains still incompletely understood. Here, the applicant proposes to investigate the role and function of the transcription factor cMaf and B lymphoid kinase (Blk) on the development of IL-17A-producing iNKT cell subset differentiation.
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| 研究実績の概要 |
The plan for the FY2021 was to generate a conditional cMaf knock-out mouse for the experiments to understand the function and role of the transcription factor cMaf on the development of iNKT cells. Currently, the newly obtained cMaf(loxP/loxP) mice are being bred at the SPF animal facility of the Kanazawa University with the CD4-Cre transgenic or Lck-Cre transgenic mice to obtain mouse models to be used in experiments.
Another plan was to establish an intracellular staining method of transcription factors such as Tbet, PLZF, RORgt, that was successfully achieved. Of note, the developed intracellular staining method allows us to stain and analyze iNKT cells from various organs such as the thymus, spleen and liver by using the multiparameter flow cytometer.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
The slight delay in the plan is related with the delays mainly due to worldwide COVID-19 situation in obtaining to the SPF facility of the Kanazawa University of genetically modified mouse models to be used in the project such as the cMaf(loxP/loxP) mouse line, Lck-Cre and CD4-Cre transgenic mouse lines.
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| 今後の研究の推進方策 |
1) Generate and analyze conditional cMaf-deficient mice to dissect the role of transription factor cMaf on the development and function of iNKT cell subsets by using multiparameter flow cytometry, where the intracellular staining of transcription factors Tbet, PLZF, RORgammat would be employed.
2) Functional tests of cMaf-deficient iNKT cells would be done, where cytokine production profiles will be analyzed by using multiplex cytokine beads assay.
3) Whole transcriptome analysis would be performed by using RNA-sequencing.
4) Generate and analyze B lymphoid kinase (Blk)-deficient mice, where the role of Blk on iNKT cell subset development and function will be investigated. RNA-sequencing of Blk-deficient iNKT cells is to be done.
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