The role of exosomes in sarcoidosis

Abstract: Sarcoidosis is a systemic inflammatory disease mostly affecting the lungs, marked by the presence of granulomas and the accumulation of interferon gamma (IFNγ)-producing T cells in the affected organs. Extracellular vesicles (EVs) are membranous vesicles with a size range of 50 nm to 5000 nm, with exosomes ranging from 50 to 150 nm. They are major players in intercellular communication and have been found in all body fluids including plasma. In this study, we wanted to characterize the exosomes from sarcoidosis patients’ plasma and try to detect differences in their surface marker expression. Additionally, we aimed to investigate the cellular origin of these exosomes in the blood circulation of mice. We used a combination of Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), Western Blot and Flow cytometry as characterization methods. Moreover, we took advantage of immune cell-specific knock-out mice (Rag KO, Ly6G-Mcl-1 KO) and examined the effect on the number of vesicles and on the marker expression levels on the vesicle surface. We showed that in Rag KO mice, that lack mature B cells and T cells, the levels of T cell markers CD4 and CD8 were decreased. No difference was detected between wild type and neutrophil KO mice on neither of the neutrophil-specific markers Ly6G and CD11b. Sarcoidosis patient plasma EVs showed lower levels of CD9 expression compared to healthy subjects. Differences were observed in a subgroup of patients, namely Löfgren syndrome patients that exhibited higher CD31 expression than the non-Löfgren patients. Overall, our data indicate a possible contribution of the immune cell-derived exosomes in the blood. Furthermore, differences detected in the sarcoidosis plasma EVs could give a better insight on the role of those exosomes during lung inflammation and provide grounds for their use as liquid tissue biomarkers.