Morissette Mathieu C, Gao Yang, Shen Pamela, Thayaparan Danya, Bérubé Jean-Christophe, Paré Peter D, Brandsma Corry-Anke, Hao Ke, Bossé Yohan, Ettinger Rachel, Herbst Ronald, Humbles Alison A, Kolbeck Roland, Zhong Nanshan, Chen Rongchang, Stämpfli Martin R
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
State Key Laboratory of Respiratory Disease, and Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Physiol Rep. 2016 Dec;4(24). doi: 10.14814/phy2.13057.
Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF Blockade of BAFF using a BAFF receptor-Fc (BAFFR-Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR-Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking.
新出现的证据表明，自身免疫过程与慢性阻塞性肺疾病（COPD）的发病机制有关。在本研究中，我们评估了吸烟者中B细胞活化因子（BAFF）的表达，并使用临床前小鼠模型研究了BAFF在香烟烟雾诱导的肺抗核抗体（ANA）和三级淋巴组织（TLT）的诱导和维持中的功能重要性。我们观察到吸烟者和暴露于香烟烟雾的小鼠中BAFF水平升高。在小鼠中，暴露于香烟烟雾4天后，肺中BAFF表达迅速诱导，并在暴露8周和24周后保持升高。肺泡巨噬细胞是BAFF的主要来源。使用BAFF受体-Fc（BAFFR-Fc）构建体阻断BAFF，在与香烟烟雾暴露同时给予时可预防肺ANA和TLT形成。在这些条件下，未观察到对肺部炎症的影响。然而，戒烟后给予BAFFR-Fc可显著减少TLT数量和ANA水平，值得注意的是，还可减少肺部中性粒细胞增多。总之，本研究首次表明BAFF在香烟烟雾诱导的肺ANA的诱导和维持中起核心作用，并表明戒烟后阻断BAFF可能对持续性炎症过程有有益影响。在本研究中，我们评估了吸烟者中B细胞活化因子（BAFF）的表达，并使用临床前小鼠模型研究了BAFF在香烟烟雾诱导的肺抗核抗体（ANA）和三级淋巴组织（TLT）的诱导和维持中的功能重要性。所呈现的数据表明，BAFF在香烟烟雾诱导的肺ANA的诱导和维持中起核心作用，并提示阻断BAFF在限制与吸烟相关的自身免疫过程方面具有治疗潜力。
