Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides a structural basis for increased alveolar antigen uptake in chronic obstructive pulmonary disease.
(2013) In Thorax 68(6). p.521-531- Abstract
- 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.... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3559745
- author
- Mori, Michiko LU ; Andersson, Cecilia K LU ; Svedberg, Kaj LU ; Glader, Pernilla LU ; Bergqvist, Anders LU ; Shikhagaie, Medya LU ; Löfdahl, Claes-Göran LU and Erjefält, Jonas LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Thorax
- volume
- 68
- issue
- 6
- pages
- 521 - 531
- publisher
- BMJ Publishing Group
- external identifiers
-
- wos:000318766000007
- pmid:23412435
- scopus:84877621052
- pmid:23412435
- ISSN
- 1468-3296
- DOI
- 10.1136/thoraxjnl-2012-202879
- language
- English
- LU publication?
- yes
- id
- b818a4ed-910f-40a9-963b-88edbec4853f (old id 3559745)
- date added to LUP
- 2016-04-01 10:11:05
- date last changed
- 2022-04-19 23:35:19
@article{b818a4ed-910f-40a9-963b-88edbec4853f,
abstract = {{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.}},
author = {{Mori, Michiko and Andersson, Cecilia K and Svedberg, Kaj and Glader, Pernilla and Bergqvist, Anders and Shikhagaie, Medya and Löfdahl, Claes-Göran and Erjefält, Jonas}},
issn = {{1468-3296}},
language = {{eng}},
number = {{6}},
pages = {{521--531}},
publisher = {{BMJ Publishing Group}},
series = {{Thorax}},
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.}},
url = {{https://lup.lub.lu.se/search/files/1633347/3674594.pdf}},
doi = {{10.1136/thoraxjnl-2012-202879}},
volume = {{68}},
year = {{2013}},
}