展开的蛋白质响应传感器IRE1调节了用病毒刺激激活体内差异化1型常规DC的激活
Bernardita Medel1, José Ignacio Bernales1, Alonso Lira1
1Laboratory of Immunology and Cellular Stress, Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
1型常规树突细胞 (cDC1s) 使用 IRE1/XBP1s 途径进行抗病毒反应. 这项研究模拟了体外IRE1激活,揭示了它在病毒刺激后在细胞因子产生中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 1型常规树突细胞 (cDC1s) 对于抗病毒免疫至关重要.
- 展开蛋白质响应 (UPR) 传感器 IRE1 和其转录因子 XBP1s 影响cDC1功能,但研究主要是体内.
- 了解控制cDC1s的细胞内机制对于免疫研究至关重要.
研究的目的:
- 为了研究在体外分化的cDC1s中的IRE1 RNase活性.
- 为了确定与病毒组件刺激的cDC1s中的IRE1激活的功能后果.
- 探索IRE1/XBP1s轴在cDC1对病毒激动剂反应中的作用.
主要方法:
- 在体外区分cDC1s.
- 刺激cDC1s与病毒模拟Poly (I:C) 进行刺激.
- 利用XBP1s的遗传删除来研究其调节作用.
主要成果:
- 在体外分化的cDC1s表现出与体内对应物相似的IRE1激活特征.
- 聚I:C) 被确定为cDC1s中的强有力的UPR诱导剂.
- 删除XBP1s导致IRE1 RNase的过度激活,并在Poly (I:C) 刺激时改变IL-12p40,TNF-α,IL-6,Ifna和Ifnb的产生.
结论:
- IRE1/XBP1s轴在cDC1激活中受到病毒激动剂的严格调节.
- 这一UPR分支对潜在的树突细胞基疗法有影响.
- 在cDC1s中IRE1活动的体外建模为免疫调节提供了洞察力.
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