德克萨米他通过上调骨髓衍生抑制细胞中的ILT4表达来促进脏纤维化
Xiaowen Gu1, Lianmei Zhang1, Min Sun2
1Department of Blood Transfusion, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Journal of cellular and molecular medicine
|April 27, 2024
概括
骨髓衍生抑制细胞 (MDSCs) 的采用转移使小鼠的纤维化恶化. 德甲通过ILT4增强了MDSC纤维化促进的细胞因子,加剧了损伤.
科学领域:
- 免疫学 免疫学 免疫学
- 腎臟病學 (nephrology) 是一種醫學專業.
- 细胞生物学 细胞生物学
背景情况:
- 骨髓原抑制细胞 (MDSC) 的采用转移对炎症性疾病有希望,但长期影响和机制尚不清楚.
- 葡萄皮质类药物诱导MDSC扩张,但它们对MDSC免疫抑制功能的影响和潜在的分子通路尚未完全理解.
研究的目的:
- 调查MDSC收养转移和葡萄糖皮质激素 (德甲) 给药对小鼠多克索鲁比诱导的焦点细分结核硬化 (FSGS) 的长期影响.
- 阐明德克萨米他影响MDSC功能和加剧纤维化的分子机制.
主要方法:
- 收养转移MDSC和高剂量德克萨米他给多克索鲁比诱导的FSGS小鼠八周.
- 评估损伤标志物 (血清肌素,蛋白尿),间歇性纤维化,原沉积和α-SMA表达.
- 对TGF-β和IL-10的MDSC表达和分泌的分析,以及免疫球蛋白样转录因子4 (ILT4) 和STAT6.6的作用.
主要成果:
- 在FSGS小鼠中,MDSCs的收养转移加剧了间胞纤维化,血清肌素增加和蛋白尿.
- 德克萨米他的使用加剧了间歇性损伤和纤维化,血清肌素增加,蛋白尿,原沉积和α-SMA表达.
- 德甲通过促进ILT4表达来增强MDSC表达和TGF-β和IL-10的分泌,从而激活STAT6并加强T细胞抑制.
结论:
- 德甲通过ILT4/STAT6通路增强MDSC介导的TGF-β和IL-10分泌,从而加剧FSGS小鼠的纤维化.
- 针对MDSC中的ILT4通路可能提供一种治疗策略,以减轻葡萄糖皮质醇诱导的纤维化.
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