以PML为媒介的核松允许在炎症条件下免疫调节介质干细胞/干细胞
Yunpeng Chu1, Zishan Jiang1, Zheng Gong1
1The Third Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Medical College, Suzhou, China.
Cell proliferation
|October 21, 2023
概括
炎症性细胞因子触发人间介质细胞 (hMSCs) 中的核变化,增强其免疫功能. 这需要PML介导的染色质松,以便有效的基因表达和免疫调节.
科学领域:
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 核配置通过组织euchromatin和 heterochromatin 影响基因表达.
- 人类介质细胞 (hMSCs) 获得强大的免疫调节功能在刺激炎症细胞因子,如IFN-γ和TNF-α.
- 细胞因子诱导的基因上调和hMSCs中全基因组核变化之间的联系仍然未被探索.
研究的目的:
- 研究由炎症性细胞因子刺激的hMSCs中的全基因组核重构.
- 在这个过程中探索前细胞白血病核体 (PML-NBs) 的作用.
- 确定PML是否对hMSCs的免疫调节功能至关重要.
主要方法:
- 在hMSCs中分析核形态和染色质结构.
- 对基因表达的评估,包括重复的DNA元素.
- 在hMSC中减少PML以评估其对免疫调节功能的影响以及急性肺损伤的体内模型.
主要成果:
- hMSCs表现出核扩大,LMNB1和LMNA/C表达减少,异染色质脱凝,以及重复性DNA的脱压.
- 被确定为细胞因子诱导的核重构的调解者.
- 在LPS引起的急性肺损伤中,PML枯竭损害了hMSC的免疫调节能力,减少了效应分子的表达,并未能防止免疫细胞透.
结论:
- 炎症性细胞因子在hMSCs中诱导显著的核重新配置.
- PML-NBs对于调解这些细胞因子诱导的核变化至关重要.
- 通过PML介导的染色质松动对于由炎症性细胞因子刺激的hMSCs的免疫调节功能至关重要.
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