{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:10:53Z","timestamp":1791461453925,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,12,31]],"date-time":"2012-12-31T00:00:00Z","timestamp":1356912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Myasthenia gravis (MG) is an autoimmune disease mediated mainly by anti\u2013acetylcholine receptor (AChR) antibodies. The thymus plays a primary role in MG pathogenesis. As we recently showed an inflammatory and antiviral signature in MG thymuses, we investigated whether pathogen\u2010sensing molecules could contribute to an anti\u2010AChR response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the effects of toll\u2010like receptor agonists on the expression of \u03b1\u2010AChR and various tissue\u2010specific antigens (TSAs) in human thymic epithelial cell (TEC) cultures. As polyinosinic\u2013polycytidylic acid (poly[I:C]), which mimics double\u2010stranded RNA (dsRNA), stimulated specifically \u03b1\u2010AChR expression, the signaling pathways involved were investigated. In parallel, we analyzed the expression of dsRNA\u2010signaling components in the thymus of MG patients, and the relevance of our data was investigated in vivo in poly(I:C)\u2010injected mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that dsRNA signaling induced by poly(I:C) specifically triggers the overexpression of \u03b1\u2010AChR in TECs and not of other TSAs. A poly(I:C) effect was also observed on MG TECs. This induction is mediated through toll\u2010like receptor 3 (TLR3) and protein kinase R (PKR), and by the release of interferon (IFN)\u2010\u03b2. In parallel, human MG thymuses also display an overexpression of TLR3, PKR, and IFN\u2010\u03b2. In addition, poly(I:C) injections specifically increase thymic expression of \u03b1\u2010AChR in wild\u2010type mice, but not in IFN\u2010I receptor knockout mice. These injections also lead to an anti\u2010AChR autoimmune response characterized by a significant production of serum anti\u2010AChR antibodies and a specific proliferation of B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Because anti\u2010AChR antibodies are highly specific for MG and are pathogenic, dsRNA\u2010signaling activation could contribute to the etiology of MG. 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