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Monocytes in sarcoidosis are potent tumour necrosis factor producers and predict disease outcome
Division of Immunology and Allergy, Dept. of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Division of Immunology and Allergy, Dept. of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Dept. of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
Division of Immunology and Allergy, Dept. of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
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2021 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 58, no 1, article id 2003468Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
European Respiratory Society , 2021. Vol. 58, no 1, article id 2003468
National Category
Respiratory Medicine and Allergy
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URN: urn:nbn:se:umu:diva-186643DOI: 10.1183/13993003.03468-2020ISI: 000697742000022PubMedID: 33446605Scopus ID: 2-s2.0-85111990276OAI: oai:DiVA.org:umu-186643DiVA, id: diva2:1586657
Available from: 2021-08-20 Created: 2021-08-20 Last updated: 2023-09-05Bibliographically approved

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Pourazar, JamshidRankin, GregoryBlomberg, Anders

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