The online version of this article (doi:10.1186/1465-9921-15-49) contains supplementary material, which is available to authorized users.
The authors have read the journal's policy and have the following conflicts: RK and AAH are full time employees of MedImmune, a wholly owned subsidiary of AstraZeneca. This does not alter the authors' adherence to all the Respiratory Research policies on sharing data and materials.
MCM was responsible for conceptualization of mouse experiments, experimentation, data analysis, and preparation of the manuscript. BNJ, JKN, DT, and PS provided support for mouse experimentation, discussion, and manuscript preparation. RNL and RK assisted discussion of data and provided feedback for the manuscript. PN provided clinical samples and provided input on experimental design and data interpretation. AAH assisted in conceptualization of experiments, discussion of data, and provided feedback for the manuscript. MRS supervised the project and played an instrumental part in conceptualizing experiments and the preparation of the manuscript. All authors read and approved the final manuscript.
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.
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- Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure
Mathieu C Morissette
Brian N Jobse
Jake K Nikota
Nancy Renée Labiris
Alison A Humbles
Martin R Stämpfli
- BioMed Central
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