Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides a structural basis for increased alveolar antigen uptake in chronic obstructive pulmonary disease
- Michiko Mori1,
- Cecilia K Andersson2,
- Kaj A Svedberg1,
- Pernilla Glader2,3,
- Anders Bergqvist2,
- Medya Shikhagaie1,
- Claes-Göran Löfdahl2,
- Jonas S Erjefält1,2
- 1Department of Experimental Medical Science, Lund University, Lund, Sweden
- 2Department of Respiratory Medicine and Allergology, Lund University Hospital, Lund, Sweden
- 3Respiratory Medicine and Allergology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Correspondence to Dr Jonas S Erjefält, Head, Unit of Airway Inflammation and Immunology, Department of Experimental Medical Science, BMC D12, Klinikgatan 30, Lund University, Lund SE-22184, Sweden;
- Received 16 October 2012
- Revised 6 January 2013
- Accepted 16 January 2013
- Published Online First 14 February 2013
Rationale 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.
Objectives 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.