Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure.
Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure.
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DOI：
10.1186/1465-9921-15-49
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发表时间：
2014-04-22
影响因子：
5.8
通讯作者：
Stämpfli MR
中科院分区：
文献类型：
--
作者：
Morissette MC;Jobse BN;Thayaparan D;Nikota JK;Shen P;Labiris NR;Kolbeck R;Nair P;Humbles AA;Stämpfli MR
肺三级免疫结构的形成是晚期COPD的特征。在目前的研究中，我们研究了香烟烟雾暴露小鼠肺中三级淋巴组织(TLT)的形成机制。我们发现，香烟烟雾暴露导致了TLT的形成，并在戒烟后持续存在。TLTS主要由IgM阳性的B细胞组成，而靠近TLTS的浆细胞表达IgM、Ig G和Ig A。TLT形成的存在与抗核自身抗体(ANA)的产生有关，这种抗体在戒烟后也持续存在。在香烟烟雾暴露的小鼠的肺中观察到了ANA，但没有观察到循环中的ANA。同样，我们在COPD患者的痰中观察到ANA水平与疾病严重程度相关，并且对类固醇治疗无效。ANA的产生和TLT的形成均依赖于IL-1受体1(IL-1R1)的表达。与TLT和ANA相反，戒烟后肺中性粒细胞减少。这些数据表明，与香烟烟雾暴露相关的先天免疫炎症过程和B细胞相关免疫炎症过程的调节存在差异。此外，我们的研究进一步强调了白介素1(IL-1)信号通路在吸烟相关肺部发病机制中的重要性。
Formation of pulmonary tertiary immune structures is a characteristic feature of advanced COPD. In the current study, we investigated the mechanisms of tertiary lymphoid tissue (TLT) formation in the lungs of cigarette smoke-exposed mice. We found that cigarette smoke exposure led to TLT formation that persisted following smoking cessation. TLTs consisted predominantly of IgM positive B cells, while plasma cells in close proximity to TLTs expressed IgM, IgG, and IgA. The presence of TLT formation was associated with anti-nuclear autoantibody (ANA) production that also persisted following smoking cessation. ANAs were observed in the lungs, but not the circulation of cigarette smoke-exposed mice. Similarly, we observed ANA in the sputum of COPD patients where levels correlated with disease severity and were refractory to steroid treatment. Both ANA production and TLT formation were dependent on interleukin-1 receptor 1 (IL-1R1) expression. Contrary to TLT and ANA, lung neutrophilia resolved following smoking cessation. These data suggest a differential regulation of innate and B cell-related immune inflammatory processes associated with cigarette smoke exposure. Moreover, our study further emphasizes the importance of interleukin-1 (IL-1) signaling pathways in cigarette smoke-related pulmonary pathogenesis.