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Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
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2019 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 105, no 4, p. 797-807Article in journal (Refereed) Published
Abstract [en]

Sarcoidosis is a T-cell driven inflammatory disease characterized by granuloma formation. Mononuclear phagocytes (MNPs)-macrophages, monocytes, and dendritic cells (DCs)-are likely critical in sarcoidosis as they initiate and maintain T cell activation and contribute to granuloma formation by cytokine production. Granulomas manifest primarily in lungs and lung-draining lymph nodes (LLNs) but these compartments are less studied compared to blood and bronchoalveolar lavage (BAL). Sarcoidosis can present with an acute onset (usually Lofgren's syndrome (LS)) or a gradual onset (non-LS). LS patients typically recover within 2 years while 60% of non-LS patients maintain granulomas for up to 5 years. Here, four LS and seven non-LS patients underwent bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). From each patient, blood, BAL, endobronchial biopsies (EBBs), and LLN samples obtained by EBUS-TBNA were collected and MNPs characterized using multicolor flow cytometry. Six MNP subsets were identified at varying frequencies in the anatomical compartments investigated. Importantly, monocytes and DCs were most mature with migratory potential in BAL and EBBs but not in the LLNs suggesting heterogeneity in MNPs in the compartments typically affected in sarcoidosis. Additionally, in LS patients, frequencies of DC subsets were lower or lacking in LLNs and EBBs, respectively, compared to non-LS patients that may be related to the disease outcome. Our work provides a foundation for future investigations of MNPs in sarcoidosis to identify immune profiles of patients at risk of developing severe disease with the aim to provide early treatment to slow down disease progression.

Place, publisher, year, edition, pages
Society for Leukocyte Biology , 2019. Vol. 105, no 4, p. 797-807
Keywords [en]
dendritic cell, monocyte, sarcoidosis, lymph node, Lofgren's syndrome
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:umu:diva-158084DOI: 10.1002/JLB.5A0718-280RRISI: 000462155000015PubMedID: 30742337OAI: oai:DiVA.org:umu-158084DiVA, id: diva2:1304909
Funder
Swedish Heart Lung FoundationSwedish Research CouncilAvailable from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-15Bibliographically approved

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Rankin, GregoryPourazar, JamshidMuala, AlaBlomberg, Anders

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