Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure

Respiratory Research

Martin R Stämpfli³  Alison A Humbles²  Parameswaran Nair¹  Roland Kolbeck²  Nancy Renée Labiris¹  Pamela Shen⁶  Jake K Nikota⁶  Danya Thayaparan⁴  Brian N Jobse⁵  Mathieu C Morissette⁵ 

[1] Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, ON, Canada;MedImmune LLC, Gaithersburg, MD, USA;MDCL 4011, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada;Honours Molecular Biology & Genetics Co-op Program, McMaster University, Hamilton, ON, Canada;Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada;Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada

关键词: Inflammation;    Experimental model;    COPD;    Autoimmunity;    Autoantibodies;    Tertiary lymphoid tissue;   

Others  :  790307
DOI  :  10.1186/1465-9921-15-49

 received in 2013-12-05, accepted in 2014-04-11,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Morissette et al.; licensee BioMed Central Ltd.

【 图 表 】

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