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Expansion of Phenotypically Altered Dendritic Cell Populations in the Small Airways and Alveolar Parenchyma in Patients with Chronic Obstructive Pulmonary Disease

Mori, Michiko LU ; Clausson, Carl Magnus LU ; Sanden, Caroline LU ; Jönsson, Jimmie ; Andersson, Cecilia K. LU ; Siddhuraj, Premkumar LU ; Shikhagaie, Medya LU ; Åkesson, Karolina ; Bergqvist, Anders LU and Löfdahl, Claes Göran LU , et al. (2023) In Journal of Innate Immunity 15(1). p.188-203
Abstract

Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex immunohistochemistry was applied to quantify langerin/CD207+, CD1a+, BDCA2+, and CD11c+ subsets in distal lung compartments from patients with COPD (GOLD stage I-IV) and never-smoking and smoking controls. In the alveolar parenchyma, increased numbers of CD1a+langerin- (p < 0.05) and BDCA-2+ DCs (p < 0.001) were observed in... (More)

Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex immunohistochemistry was applied to quantify langerin/CD207+, CD1a+, BDCA2+, and CD11c+ subsets in distal lung compartments from patients with COPD (GOLD stage I-IV) and never-smoking and smoking controls. In the alveolar parenchyma, increased numbers of CD1a+langerin- (p < 0.05) and BDCA-2+ DCs (p < 0.001) were observed in advanced COPD compared with controls. Alveolar CD11c+ DCs also increased in advanced COPD (p < 0.01). In small airways, langerin+ and BDCA-2+ DCs were also significantly increased. Contrasting the small airway DCs, most alveolar DC subsets frequently extended luminal protrusions. Importantly, alveolar and small airway langerin+ DCs in COPD lungs displayed site-specific marker profiles. Further, multiplex immunohistochemistry with single-cell quantification was used to specifically profile langerin DCs and reveal site-specific expression patterns of the maturation and activation markers S100, fascin, MHC2, and B7. Taken together, our results show that clinically advanced COPD is associated with increased levels of multiple alveolar DC populations exhibiting features of both adaptive and innate immunity phenotypes. This expansion is likely to contribute to the distal lung immunopathology in COPD patients.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antigen presentation, Immune pathology, Peripheral lung
in
Journal of Innate Immunity
volume
15
issue
1
pages
16 pages
publisher
Karger
external identifiers
  • pmid:35998572
  • scopus:85180225582
ISSN
1662-811X
DOI
10.1159/000526080
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 S. Karger AG. All rights reserved.
id
0f4b7f20-0cfb-4863-8de8-06897063c0cd
date added to LUP
2026-07-02 15:00:55
date last changed
2026-07-02 15:01:37
@article{0f4b7f20-0cfb-4863-8de8-06897063c0cd,
  abstract     = {{<p>Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex immunohistochemistry was applied to quantify langerin/CD207+, CD1a+, BDCA2+, and CD11c+ subsets in distal lung compartments from patients with COPD (GOLD stage I-IV) and never-smoking and smoking controls. In the alveolar parenchyma, increased numbers of CD1a+langerin- (p &lt; 0.05) and BDCA-2+ DCs (p &lt; 0.001) were observed in advanced COPD compared with controls. Alveolar CD11c+ DCs also increased in advanced COPD (p &lt; 0.01). In small airways, langerin+ and BDCA-2+ DCs were also significantly increased. Contrasting the small airway DCs, most alveolar DC subsets frequently extended luminal protrusions. Importantly, alveolar and small airway langerin+ DCs in COPD lungs displayed site-specific marker profiles. Further, multiplex immunohistochemistry with single-cell quantification was used to specifically profile langerin DCs and reveal site-specific expression patterns of the maturation and activation markers S100, fascin, MHC2, and B7. Taken together, our results show that clinically advanced COPD is associated with increased levels of multiple alveolar DC populations exhibiting features of both adaptive and innate immunity phenotypes. This expansion is likely to contribute to the distal lung immunopathology in COPD patients.</p>}},
  author       = {{Mori, Michiko and Clausson, Carl Magnus and Sanden, Caroline and Jönsson, Jimmie and Andersson, Cecilia K. and Siddhuraj, Premkumar and Shikhagaie, Medya and Åkesson, Karolina and Bergqvist, Anders and Löfdahl, Claes Göran and Erjefält, Jonas S.}},
  issn         = {{1662-811X}},
  keywords     = {{Antigen presentation; Immune pathology; Peripheral lung}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  pages        = {{188--203}},
  publisher    = {{Karger}},
  series       = {{Journal of Innate Immunity}},
  title        = {{Expansion of Phenotypically Altered Dendritic Cell Populations in the Small Airways and Alveolar Parenchyma in Patients with Chronic Obstructive Pulmonary Disease}},
  url          = {{http://dx.doi.org/10.1159/000526080}},
  doi          = {{10.1159/000526080}},
  volume       = {{15}},
  year         = {{2023}},
}