title: Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure.
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.
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Morissette
authors.forename: Brian N
authors.initials: BN
authors.lastname: Jobse
authors.forename: Danya
authors.initials: D
authors.lastname: Thayaparan
authors.forename: Jake K
authors.initials: JK
authors.lastname: Nikota
authors.forename: Pamela
authors.initials: P
authors.lastname: Shen
authors.forename: Nancy Renée
authors.initials: NR
authors.lastname: Labiris
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada. stampfli@mcmaster.ca.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D000368:Aged; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism* / Q000473:pathology; D016540:Smoking Cessation; D013183:Sputum / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000974:Antibodies, Antinuclear
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