Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Respiratory Medicine Unit, Department of Medicine and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Clin Immunol. 2016 Aug;169:114-120. doi: 10.1016/j.clim.2016.06.006. Epub 2016 Jun 23.
Cigarette smoking is a risk factor for multiple sclerosis (MS), and the risk is further multiplied for HLA-DRB115(+) smokers. To define the smoke-induced immune responses in the lung we performed bronchoscopy with bronchoalveolar lavage (BAL) on smokers and non-smokers, both MS-patients and healthy volunteers. In the BAL, non-smokers with MS showed an increased preformed CD40L expression in CD4(+) T-cells while smokers displayed an increase in proliferating (Ki-67(+)) T-cells. In addition, our results confirm that smoking induces an increase of alveolar macrophages in BAL, and further defined a significant attenuation of this response in carriers of the HLA-DRB115 allele, in both MS patients and healthy controls. This first systematic investigation of the immune response in the lungs of smokers and non-smokers diagnosed with MS, thus suggests an MS-associated lung T-cell phenotype, involvement of a specific T-cell response to smoke, and a genetic regulation of the macrophage response.
吸烟是多发性硬化症（MS）的一个风险因素，而对于携带 HLA-DRB115（+）的吸烟者来说，风险会进一步增加。为了定义吸烟引起的肺部免疫反应，我们对吸烟者和非吸烟者（包括 MS 患者和健康志愿者）进行了支气管镜检查和支气管肺泡灌洗（BAL）。在 BAL 中，MS 非吸烟者的 CD4(+) T 细胞中预先存在的 CD40L 表达增加，而吸烟者的增殖（Ki-67(+））T 细胞增加。此外，我们的结果证实，吸烟会诱导 BAL 中肺泡巨噬细胞的增加，并且在 HLA-DRB115 等位基因携带者中，这种反应明显减弱，无论是在 MS 患者还是健康对照组中都是如此。这项对诊断为 MS 的吸烟者和非吸烟者肺部免疫反应的首次系统研究表明，存在与 MS 相关的肺部 T 细胞表型，涉及到对烟雾的特定 T 细胞反应，以及巨噬细胞反应的遗传调控。
