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The thymus plays a primary role in AChR\u2010MG and is characterized by a type I interferon (IFN) signature linked to IFN\u2010\u03b2. We investigated if AChR\u2010MG was characterized by an IFN\u2010I signature in the blood, and further investigated the chronic thymic IFN\u2010I signature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum levels of IFN\u2010\u03b2 and IFN\u2010\u03b1 subtypes, and mRNA expression for IFN\u2010I subtypes and IFN\u2010stimulated genes in peripheral mononuclear blood cells (PBMCs) were analyzed. The contribution of endogenous nucleic acids in thymic expression of IFN\u2010I subtypes was investigated in human thymic epithelial cell cultures and the mouse thymus. By immunohistochemistry, thymic CD68<jats:sup>+<\/jats:sup> and CD163<jats:sup>+<\/jats:sup> macrophages were analyzed in AChR\u2010MG. To investigate the impact of a decrease in thymic macrophages, mice were treated with an anti\u2010CSF1R antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No IFN\u2010I signature was observed in the periphery emphasizing that the IFN\u2010I signature is restricted to the MG thymus. Molecules mimicking endogenous dsDNA signalization (Poly(dA:dT) and 2\u20323\u2032\u2010cGAMP), or dexamethasone\u2010induced necrotic thymocytes increased IFN\u2010\u03b2 and \u03b1\u2010AChR expression by thymic epithelial cells, and in the mouse thymus. A significant decrease in thymic macrophages was demonstrated in AChR\u2010MG. In mice, a decrease in thymic macrophages led to an increase of necrotic thymocytes associated with IFN\u2010\u03b2 and \u03b1\u2010AChR expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results suggest that the decrease of thymic macrophages in AChR\u2010MG impairs the elimination of apoptotic thymocytes favoring the release of endogenous nucleic acids from necrotic thymocytes. In this inflammatory context, thymic epithelial cells may overexpress IFN\u2010\u03b2, which specifically induces \u03b1\u2010AChR, resulting in self\u2010sensitization and thymic changes leading to AChR\u2010MG. 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