Monocytes in sarcoidosis are potent tumour necrosis factor producers and predict disease outcome.
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
11
09
2020
accepted:
17
12
2020
pubmed:
16
1
2021
medline:
10
8
2021
entrez:
15
1
2021
Statut:
epublish
Résumé
Pulmonary sarcoidosis is an inflammatory disease characterised by granuloma formation and heterogeneous clinical outcome. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells, which are poorly studied in sarcoidosis, despite their central role in inflammation. To determine the role of pulmonary monocyte-derived cells and dendritic cells during sarcoidosis. We performed in-depth phenotypic, functional and transcriptomic analysis of MNP subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls. We followed the clinical development of patients and assessed how the repertoire and function of MNP subsets at diagnosis correlated with 2-year disease outcome. Monocytes/monocyte-derived cells were increased in blood and BAL of sarcoidosis patients compared to healthy controls. Interestingly, high frequencies of blood intermediate monocytes at time of diagnosis associated with chronic disease development. RNA sequencing analysis showed highly inflammatory MNPs in BAL of sarcoidosis patients. Furthermore, frequencies of BAL monocytes/monocyte-derived cells producing TNF without exogenous stimulation at time of diagnosis increased in patients that were followed longitudinally. In contrast to alveolar macrophages, the frequency of TNF-producing BAL monocytes/monocyte-derived cells at time of diagnosis was highest in sarcoidosis patients that developed progressive disease. Our data show that pulmonary monocytes/monocyte-derived cells are highly inflammatory and can be used as a predictor of disease outcome in sarcoidosis patients.
Sections du résumé
BACKGROUND
Pulmonary sarcoidosis is an inflammatory disease characterised by granuloma formation and heterogeneous clinical outcome. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells, which are poorly studied in sarcoidosis, despite their central role in inflammation.
OBJECTIVE
To determine the role of pulmonary monocyte-derived cells and dendritic cells during sarcoidosis.
METHODS
We performed in-depth phenotypic, functional and transcriptomic analysis of MNP subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls. We followed the clinical development of patients and assessed how the repertoire and function of MNP subsets at diagnosis correlated with 2-year disease outcome.
RESULTS
Monocytes/monocyte-derived cells were increased in blood and BAL of sarcoidosis patients compared to healthy controls. Interestingly, high frequencies of blood intermediate monocytes at time of diagnosis associated with chronic disease development. RNA sequencing analysis showed highly inflammatory MNPs in BAL of sarcoidosis patients. Furthermore, frequencies of BAL monocytes/monocyte-derived cells producing TNF without exogenous stimulation at time of diagnosis increased in patients that were followed longitudinally. In contrast to alveolar macrophages, the frequency of TNF-producing BAL monocytes/monocyte-derived cells at time of diagnosis was highest in sarcoidosis patients that developed progressive disease.
CONCLUSION
Our data show that pulmonary monocytes/monocyte-derived cells are highly inflammatory and can be used as a predictor of disease outcome in sarcoidosis patients.
Identifiants
pubmed: 33446605
pii: 13993003.03468-2020
doi: 10.1183/13993003.03468-2020
pmc: PMC8295505
pii:
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright ©The authors 2021.
Déclaration de conflit d'intérêts
Conflict of interest: R. Lepzien has nothing to disclose. Conflict of interest: S. Liu has nothing to disclose. Conflict of interest: P. Czarnewski has nothing to disclose. Conflict of interest: M. Nie has nothing to disclose. Conflict of interest: B. Österberg has nothing to disclose. Conflict of interest: F. Baharom has nothing to disclose. Conflict of interest: J. Pourazar has nothing to disclose. Conflict of interest: G. Rankin has nothing to disclose. Conflict of interest: A. Eklund has nothing to disclose. Conflict of interest: M. Bottai has nothing to disclose. Conflict of interest: S. Kullberg has nothing to disclose. Conflict of interest: A. Blomberg has nothing to disclose. Conflict of interest: J. Grunewald has nothing to disclose. Conflict of interest: A. Smed-Sörensen reports grants from Swedish Heart-Lung Foundation, Swedish Research Council and Karolinska Institutet, during the conduct of the study.