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Identifier |
000399142 |
Title |
Identification of the effect of IFNa on the mitophagy pathway and the autoreactive phenotype of peripheral blood monocytes in the context of SLE |
Alternative Title |
Διερεύνηση της επίδρασης της ιντερφερόνης-α στο μονοπάτι μιτοφαγίας και στον αυτοδραστικό φαινότυπο των μονοκυττάρων περιφερικού αίματος στο πλαίσιο του ΣΛΕ |
Author
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Μπλανάς, Αθανάσιος
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Thesis advisor
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Μπερτσιάς, Γ.
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Reviewer
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Βεργίνης, Π.
Σπηλιανάκης, Χ.
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Abstract |
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder, predominantly affecting females in which loss of tolerance to nucleic acids (as well as their interacting proteins) results in the production of pathogenic autoantibodies that cause inflammation and tissue damage. The pathogenic role of type I IFNs in SLE is supported by a signature of IFNa-induced genes in circulating immune cells of the peripheral blood of active SLE patients and from high IFNa serum levels in these patients, which reflects to disease activity and severity. Autoreactive monocytes in SLE, the prototype autoimmune disease in humans, are characterized by IFNa-DC phenotype and their differentiation and self-antigen presentation by major histocompatibility class (MHC-) II proteins has been shown to depend on cellular macroautophagy. Autophagy is a cellular catabolic process that involves degradation of unnecessary or dysfunctional cellular components and relies on the cooperation of autophagosomes with lysosomes. Furthermore, mitophagy is a selective form of autophagy, responsible for the removal of excess or defective mitochondria of the cell. During this project we will examine a possible link between IFNa signaling and mitophagy regulation in SLE monocytes and investigate its potent impact on the autoreactive phenotype of monocytes and the disturbance of self content clearance. Specifically, we will try to find the origin of dsDNA autoantigens -characteristic of human SLE- and simultaneously dissect one of the mechanisms that may result in the generation of an immunogenic pool of self antigens and their successful presentation. Therefore, the present study aims to focus for the very first time on a symbiotic but at the same time immunogenic prokaryotic nucleic acid, mitochondrial DNA.
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Language |
English |
Subject |
Autophagy |
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Interferon-A |
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Mitochondria |
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Μιτοχόνδρια |
Issue date |
2015-12-8 |
Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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Views |
210 |