Transcriptional characterization of mononuclear phagocytes (MNP) in blood and BAL of healthy and sarcoidosis patients

Pulmonary sarcoidosis is an inflammatory disease characterized by granuloma formation and heterogeneous clinical outcome. TNF is a proinflammatory 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 (AMs) have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells (DCs) that despite their central role in inflammation are poorly studied in sarcoidosis. We performed in-depth phenotypic, functional and transcriptomic analysis of MNPs subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls. 108 sarcoidosis patients and 30 healthy volunteers were included in the study and gave written informed consent. All patients were newly diagnosed with pulmonary sarcoidosis as defined by WASOG guidelines based on clinical signs, chest radiography findings, an elevated CD4/CD8 T cell ratio in BAL, or non-caseating granulomas in tissue biopsies. Blood and BAL was processed within one hour after retrieval for further applications. Peripheral blood mononuclear cells (PBMCs) were isolated from blood using Ficoll density gradient centrifugation.