Exosomes From Subjects With Multiple Sclerosis Express EBV-Derived Proteins and Activate Monocyte-Derived Macrophages.

Autor:	Mrad MF; From the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon., Saba ES; From the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon., Nakib L; From the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon., Khoury SJ; From the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon. sk88@aub.edu.lb.
Jazyk:	angličtina
Zdroj:	Neurology(R) neuroimmunology & neuroinflammation [Neurol Neuroimmunol Neuroinflamm] 2021 May 18; Vol. 8 (4). Date of Electronic Publication: 2021 May 18 (Print Publication: 2021).
DOI:	10.1212/NXI.0000000000001004
Abstrakt:	Objective: To investigate in a cross-sectional study the effect of serum-derived exosomes on primary human blood monocyte-derived macrophages (MDMs) comparing exosomes from healthy donors vs patients with relapsing-remitting multiple sclerosis in remission and in relapse and to assess whether the response correlates with exosomal Epstein-Barr virus (EBV) protein expression. Methods: A total of 45 serum-derived exosome preparations were isolated from patients and healthy controls and verified for the expression of exosomal and EBV markers. MDMs were differentiated from monocytes for 7 days and incubated for 24 hours with exosomes, and then, cell supernatants were collected for cytokine measurement by cytometric bead array. Cells were immunophenotyped before and after differentiation. Results: Serum-derived exosomes of patients with multiple sclerosis (MS) expressed higher levels of EBV proteins than healthy controls. Of interest, expression of EBV nuclear antigen EBNA1 and latent membrane proteins LMP1 and 2A was higher on exosomes derived from patients with active RRMS compared with healthy controls and stable patients. After data normalization, we observed that incubation with EBV(+) exosomes induced CXCL10 and CCL2 secretion by MDMs. MDMs differentiated from patients with active disease were better secretors of CXCL10 and other interferon-γ-inducible chemokines, including CCL2 and CXCL9, than MDMs from healthy and stable MS groups. MDMs from active patients had a higher frequency of a CD14(++) subset that correlated with the secreted CXCL10. Conclusion: Exosomes expressing EBV proteins correlate with disease activity and induce an inflammatory response in MDMs that is compounded by the origin of the responder cells. (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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