Smoking Impairs the Immunomodulatory Capacity of Lung-Resident Mesenchymal Stem Cells in Chronic Obstructive Pulmonary Disease
Smoking Impairs the Immunomodulatory Capacity of Lung-Resident Mesenchymal Stem Cells in Chronic Obstructive Pulmonary Disease
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DOI：
10.1165/rcmb.2018-0351oc
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发表时间：
2019-11-01
影响因子：
6.4
通讯作者：
Faner, Rosa
中科院分区：
文献类型：
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作者：
Cruz, Tamara;Lopez-Giraldo, Alejandra;Faner, Rosa
吸烟是慢性阻塞性肺疾病（COPD）的主要环境危险因素，但并非所有吸烟者都会患上这种疾病。健康的肺中存在一群肺驻留间充质干细胞（LR-MSCs），但吸烟如何影响它们以及它们在COPD中的作用尚未得到评估。使用基于球的培养技术，我们从非吸烟者和当前和以前吸烟者（有和没有COPD）的肺组织中分离LR-MSC（n = 53）。通过流式细胞术和Affyssin阵列表征细胞。他们的免疫调节能力进行了评估，在体外使用与T细胞的共培养物和预孵育后，与2.5%和5%的香烟烟雾提取物。我们能够在所有研究组中分离出表达相似表型标志物的LR-MSC。来自目前吸烟的COPD患者的LR-MSCs表达不同水平的CX 3CL 1和CCL 5细胞因子，并且不能调节CD 8（+）T细胞增殖。用香烟烟雾提取物预孵育LR-MSCs降低了它们的免疫调节能力。总之，1）LR-MSC可以以相似的量从从不吸烟者和吸烟者中分离出，无论是否患有COPD; 2）它们的免疫调节能力在患有COPD的当前吸烟者中受损，但在肺功能正常的吸烟者中不受损; 3）这在戒烟后是可逆的，并且在体外是可再现的。
Tobacco smoking is the main environmental risk factor for chronic obstructive pulmonary disease (COPD), but not all smokers develop the disease. A population of lung-resident mesenchymal stem cells (LR-MSCs) exist in healthy lungs, but how tobacco smoking affects them and their role in COPD have not been assessed yet. Using a sphere-based culture technique, we isolated LR-MSCs from lung tissue obtained from nonsmokers and current and former smokers with and without COPD (n = 53). The cells were characterized by flow cytometry and Affymetrix arrays. Their immunomodulatory capacity was assessed in vitro using cocultures with T cells and after preincubation with 2.5% and 5% cigarette smoke extract. We were able to isolate LR-MSCs expressing similar phenotypic markers in all of the study groups. LR-MSCs from current smokers with COPD expressed different levels of CX3CL1 and CCL5 cytokines, and were unable to modulate CD8(+) T-cell proliferation. Preincubation of LR-MSCs with cigarette smoke extract reduced their immunomodulatory capacity. In conclusion, 1) LR-MSCs can be isolated in similar amounts from never-smokers and smokers with and without COPD; 2) their immunomodulatory capacity is impaired in current smokers with COPD, but not in those with normal lung function; and 3) this is reversible after smoking cessation and is reproducible in vitro.