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LXR依存遺伝子の発現は,マクロファージの生存と先天的な免疫反応にとって重要です
Sean B Joseph1, Michelle N Bradley, Antonio Castrillo
1Howard Hughes Medical Institute and Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
Cell
|October 14, 2004
まとめ
肝臓X受容体 (LXRs) は,脂質代謝を調節し,先天的免疫に影響を与える. LXR欠乏したマウスは,マクロファージの機能障害とアポトーシスによるListeria monocytogenes感染に対する感受性の増加を示しています.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 肝臓X受容体 (LXR) は,脂質代謝に関与する核受容体として知られています.
- 免疫反応,特にマクロファージにおけるそれらの役割は,あまり理解されていない.
研究 の 目的:
- 細菌感染中のマクロファージの機能におけるLXRシグナル伝達の役割を調査する.
- LXR欠乏が宿主防御に対するListeria monocytogenesに対する影響を決定する.
主な方法:
- 機能的なLXRを欠いたマウスモデルを使用した.
- マクロファージに依存する感受性を評価するために骨髄移植の研究を行った.
- マクロファージのアポプトーシスとバクテリアのクリアランスをin vitroとin vivoで分析した.
- LXRalpha.によって抗アポプトシス因子SPalphaの調節を調査しました.
主要な成果:
- LXRsが欠けているマウスは,Listeria monocytogenes感染に対する感受性が高くなります.
- LXR-nullマクロファージは,アポトーシスの加速とバクテリアの欠陥クリアランスを示します.
- LXRalphaの直接標的であるSPalphaは,感染中にアポトーシスを抑制する上で重要な役割を果たしています.
- マクロファージのLXRalphaまたはSPalpha発現を回復することは,アポトーシスを軽減します.
結論:
- LXRシグナル伝達は,先天性免疫とマクロファージの抗菌反応に不可欠である.
- LXR依存遺伝子発現は,細胞内病原体に対する宿主の防御に影響を与えます.
- 核受容体の経路は,脂質タンパク質と病原体に対するマクロファージの反応を媒介する.
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