Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation.
TGF-β1
blood
bronchoalveolar lavage
chronic obstructive pulmonary disease
impaired immune activation
macrophage
monocyte
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
10
04
2022
accepted:
24
06
2022
entrez:
18
8
2022
pubmed:
19
8
2022
medline:
20
8
2022
Statut:
epublish
Résumé
Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-β1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.
Identifiants
pubmed: 35979364
doi: 10.3389/fimmu.2022.917232
pmc: PMC9377018
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
917232Subventions
Organisme : NIMH NIH HHS
ID : U19 MH114821
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA217377
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118672
Pays : United States
Informations de copyright
Copyright © 2022 Baßler, Fujii, Kapellos, Dudkin, Reusch, Horne, Reiz, Luecken, Osei-Sarpong, Warnat-Herresthal, Bonaguro, Schulte-Schrepping, Wagner, Günther, Pizarro, Schreiber, Knoll, Holsten, Kröger, De Domenico, Becker, Händler, Wohnhaas, Baumgartner, Köhler, Theis, Kraut, Wadsworth, Hughes, Ferreira, Hinkley, Kaltheuner, Geyer, Thiele, Shalek, Feißt, Thomas, Dickten, Beyer, Baum, Yosef, Aschenbrenner, Ulas, Hasenauer, Theis, Skowasch and Schultze.
Déclaration de conflit d'intérêts
The handling editor [AH] declared a shared affiliation with the author(s) [AW, NY] at the time of review. BR, FB, MK and HD were employed by CommaSoft. CW and PB were employed by Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.
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