Abstract
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.
Highlights
Cigarette smoking is well know for its adverse health impacts, being a leading risk factor for most cancers, as well as cardiovascular and respiratory diseases [1]
Chronic cigarette smoke exposure leads to persistent tertiary lymphoid tissue formation in the lung A characteristic histopathological feature of advanced chronic obstructive pulmonary disease (COPD) is the emergence of pulmonary tertiary lymphoid tissue (TLT) [16]
No TLT formation was observed in agematched room air-exposed animals, providing evidence that formation of these lymphoid structures was a consequence of cigarette smoke exposure rather than aging
Summary
Cigarette smoking is well know for its adverse health impacts, being a leading risk factor for most cancers, as well as cardiovascular and respiratory diseases [1]. Emphasis has been placed on reducing smoking prevalence; a greater understanding of the mechanisms of cigarette smoke’s adverse effects on human health is relevant given the addictive nature and chronic persistence of cigarette smoking, and the burden tobacco use places on healthcare [1]. It is widely accepted that inflammatory processes elicited by cigarette smoke play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cytokines play a key role in orchestrating cigarette smoke-induced inflammatory processes. More than 50 cytokines and chemokines of interest have been reported [9].
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