title: Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides a structural basis for increased alveolar antigen uptake in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  The alveolar pathology in chronic obstructive pulmonary disease (COPD) involves antigen-driven immune events. However, the induction sites of alveolar adaptive immune responses have remained poorly investigated.
  
  
  OBJECTIVE
  To explore the hypothesis that interfaces between the alveolar lumen and lymphoid aggregates (LAs) provide a structural basis for increased alveolar antigen uptake in COPD lungs.
  
  
  METHODS
  Lung samples from patients with mild (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), moderate-severe (GOLD II-III), and very severe (GOLD IV) COPD were subjected to detailed histological assessments of adaptive immune system components. Never smokers and smokers without COPD served as controls.
  
  
  RESULTS
  Quantitative histology, involving computerised three-dimensional reconstructions, confirmed a rich occurrence of alveolar-restricted LAs and revealed, for the first time, that the vast majority of vascular or bronchiolar associated LAs had alveolar interfaces but also an intricate network of lymphatic vessels. Uniquely to COPD lungs, the interface epithelium had transformed into a columnar phenotype. Accumulation of langerin (CD207)(+) dendritic cells occurred in the interface epithelium in patients with COPD but not controls. The antigen-capturing capacity of langerin(+) dendritic cells was confirmed by increased alveolar protrusions and physical T cell contact. Several of these immune remodelling parameters correlated with lung function parameters.
  
  
  CONCLUSIONS
  Severe stages of COPD are associated with an emergence of remodelled and dendritic cell-rich alveolar-lymphoid interfaces. This novel type of immune remodelling, which predicts an increased capacity to respond to alveolar antigens, is suggested to contribute to aggravated inflammation in COPD.
authors: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Michiko
authors: M
authors: Mori
authors: Cecilia K
authors: CK
authors: Andersson
authors: Kaj A
authors: KA
authors: Svedberg
authors: Pernilla
authors: P
authors: Glader
authors: Anders
authors: A
authors: Bergqvist
authors: Medya
authors: M
authors: Shikhagaie
authors: Claes-Göran
authors: CG
authors: Löfdahl
authors: Jonas S
authors: JS
authors: Erjefält
mesh_terms: D000328:Adult; D000368:Aged; D056809:Alveolar Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000941:Antigens
keywords: COPD Mechanisms; COPD Pathology