Bi(o)communications among peripheral blood fractions: A focus on NK and NKT cell biology in rheumatoid arthritis
Bi(o)communications among peripheral blood fractions: A focus on NK and NKT cell biology in rheumatoid arthritis
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DOI：
10.3109/08916934.2012.755959
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发表时间：
2013-06-01
期刊：
影响因子：
3.5
通讯作者：
Bhatnagar, Archana
中科院分区：
文献类型：
--
作者：
Aggarwal, Ashish;Sharma, Aman;Bhatnagar, Archana
类风湿性关节炎（RA）是一种自身免疫性疾病，其病理生理机制尚不清楚，涉及许多相互交织的信号级联反应。ROS、NK和NKT细胞可能在RA的病情严重程度中起关键作用，其中NK和NKT细胞的作用在文献中存在争议。然而，氧化应激的作用，其对NK和NKT细胞免疫生物学和疾病活动（DAS 28）的影响在很大程度上是未知的。因此，我们研究了氧化应激和NK细胞亚群在RA发病机制中的作用。分析了各种外周血组分中的氧化应激状态、NK和NKT细胞表达百分比、其改变的涉及线粒体膜电位的凋亡信号通路、FAS相关死亡结构域（FADD）介导的通路和DNA损伤。结果表明，RA患者外周血中存在严重的氧化应激状态，其中NK和NKT细胞亚群的百分比减少，而ROS水平增加。患者除极线粒体膜电位、FAS、FASL及活性caspase-3阳性NK和NKT细胞亚群均显著升高。DNA损伤（以彗星尾中DNA的百分比评估）显著升高。目前的工作结果表明，增加的外周NK和NKT细胞的凋亡的疾病条件。PBMC和RBC是氧化应激增强的主要部位。NK和NKT细胞的氧化应激状态和免疫生物学改变与疾病活动评分密切相关。本研究强烈支持NK细胞亚群在RA发病机制中的保护作用。
Rheumatoid Arthritis (RA) is an autoimmune disease with unknown pathophysiology involving many interwoven signalling cascades. ROS, NK and NKT cells might be crucial in the disease severity of RA of which the role of NK and NKT cells are controversial in literature. However, the role of oxidative stress, its impact on NK and NKT cell immunobiology and disease activity (DAS28) is largely unknown. Therefore, we studied the role of oxidative stress and NK cell subsets in the pathogenesis of RA. The state of oxidative stress in various peripheral blood fractions, percentage NK and NKT cell expression, their altered apoptotic signaling pathways involving mitochondrial membrane potential, FAS associated death domain (FADD) mediated pathways and DNA damage were analyzed. Results indicated a state of profound oxidative stress in the peripheral blood of RA patients where percentage of NK and NKT cell subsets diminished while ROS levels increased. The depolarized mitochondrial membrane potential, FAS, FASL and active caspase-3 positive NK and NKT cell subsets were considerably elevated in patients. The DNA damage, assessed as percentage of DNA in comet tail, was significantly elevated. Findings of the present work indicate increased apoptosis of peripheral NK and NKT cells in the diseased condition. PBMC and RBC are the major sites of enhanced oxidative stress. The state of oxidative stress and altered immunobiology of NK and NKT cells strongly correlated with Disease activity score. The present study strongly supports the protective role of NK cell subsets in the pathogenesis of RA.