Fundación Investigación Sanitaria Illes Balears (FISIB), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Centro de investigación biomédica en red de enfermedades respiratorias (CIBERES), Mallorca, Spain.
Respir Med. 2013 Dec;107(12):1895-903. doi: 10.1016/j.rmed.2013.08.002. Epub 2013 Aug 28.
Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor ζ chain (TCR ζ) through the catabolism of l-arginine. The effects of smoking on MDSCs and their potential participation in COPD immunopathogenesis have not been explored so far.
To investigate it, we compared the level of circulating Lineage-/HLA-DR-/CD33+/CD11b+ MDSCs, the serum concentration of arginase I (ARG I) and the expression of peripheral T-cell receptor ζ chain (TCR ζ) in never smokers, smokers with normal spirometry and COPD patients. Flow cytometry was used to quantify circulating MDSCs and TCR ζ expression. Serum ARG I levels were determined by ELISA.
The main findings of this study were that: (1) current smoking upregulates and activates circulating MDSCs both in smoker controls and COPD patients; and, (2) at variance with the smokers with normal spirometry, in patients with COPD this effect persists after quitting smoking and is accompanied by a significant and specific down-regulation of the TCR ζ chain expression in circulating T lymphocytes.
Smoking modulates circulating MDSCs. Their regulation appears altered in patients with COPD.
慢性阻塞性肺疾病（COPD）的特征是对吸烟的先天和获得性免疫反应增强和持续。髓系来源的抑制细胞（MDSCs）通过代谢 l-精氨酸下调 T 细胞受体 ζ 链（TCR ζ）来调节 T 细胞反应。迄今为止，吸烟对 MDSCs 的影响及其在 COPD 发病机制中的潜在参与尚未得到探索。
为了研究这一点，我们比较了从未吸烟者、肺功能正常的吸烟者和 COPD 患者循环中的谱系-/HLA-DR-/CD33+/CD11b+MDSCs 水平、血清精氨酸酶 I（ARG I）浓度和外周 T 细胞受体 ζ 链（TCR ζ）的表达。流式细胞术用于定量循环 MDSCs 和 TCR ζ 表达。通过 ELISA 测定血清 ARG I 水平。
这项研究的主要发现是：（1）目前吸烟可上调和激活循环 MDSCs，无论是在吸烟者对照组还是 COPD 患者中；（2）与肺功能正常的吸烟者不同，在 COPD 患者中，这种效应在戒烟后仍然存在，并伴有循环 T 淋巴细胞中 TCR ζ 链表达的显著和特异性下调。
吸烟可调节循环 MDSCs。它们的调节在 COPD 患者中似乎发生了改变。
