活跃的青少年系统性红斑狼与明显的NK细胞转录和表型变化有关
Anna Radziszewska1,2, Hannah Peckham3,4, Nina M de Gruijter3,4
1Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, London, UK. ania.radziszewska@ucl.ac.uk.
Scientific reports
|June 6, 2024
概括
自然杀手 (NK) 细胞在青少年系统性红斑狼 (JSLE) 患者中减少,与疾病活性相关. 增加的亡可能解释NK细胞的这种缺陷,影响JSLE.
科学领域:
- 免疫学 免疫学 免疫学
- 这是一种自身免疫力.
- 儿科风湿病学 儿科风湿病学
背景情况:
- 系统性红斑狼 (SLE) 的适应性免疫得到了充分的研究.
- 天然杀手 (NK) 细胞在SLE病变,特别是青少年发病SLE (JSLE) 中的作用尚不清楚.
- 关于NK细胞参与SLE的证据有限且矛盾.
研究的目的:
- 研究青年发病SLE (JSLE) 中NK细胞的表型和功能.
- 为了确定NK细胞种群与JSLE疾病活性之间的关联.
- 探索JSLE中NK细胞变化的基础分子机制.
主要方法:
- 在大量JSLE患者队列中分析NK细胞表型和功能.
- 来自JSLE患者的NK细胞的转录组分析,其疾病活性和健康对照的不同.
- 途径和基因组丰富分析以确定差异表达的基因和途径.
主要成果:
- 与对照组相比,JSLE患者的总NK细胞和表达孔素和大酶A的群体显著减少.
- 减少NK细胞频率与JSLE中疾病活性增加有关.
- 转录组分析显示,疾病活动是差异性NK细胞基因表达的主要驱动因素.
- 在活跃的JSLENK细胞中观察到干扰素α反应的升调和表细胞分裂的降调.
- 亡途径在患有活性JSLE.患者的NK细胞中过度表现.
结论:
- NK细胞缺乏,特别是在表达细胞毒性分子的种群中,是JSLE的一个特征.
- 疾病活动显著影响JSLE中的NK细胞基因表达.
- 增加对亡的敏感性可能有助于在JSLE中观察到的NK细胞减少.
- 这些发现凸显了NK细胞功能障碍在JSLE病变发生过程中的潜在作用.
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