{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:30:57Z","timestamp":1792099857993,"version":"4.4.0"},"reference-count":84,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"18","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:p>\n                    In mammals, males and females show marked differences in immune responses. Males are globally more sensitive to infectious diseases, while females are more susceptible to systemic autoimmunity. X-chromosome inactivation (XCI), the epigenetic mechanism ensuring the silencing of one X in females, may participate in these sex biases. We perturbed the expression of the trigger of XCI, the noncoding RNA\n                    <jats:italic>Xist<\/jats:italic>\n                    , in female mice. This resulted in reactivation of genes on the inactive X, including members of the Toll-like receptor 7 (TLR7) signaling pathway, in monocyte\/macrophages and dendritic and B cells. Consequently, female mice spontaneously developed inflammatory signs typical of lupus, including anti\u2013nucleic acid autoantibodies, increased frequencies of age-associated and germinal center B cells, and expansion of monocyte\/macrophages and dendritic cells. Mechanistically, TLR7 signaling is dysregulated in macrophages, leading to sustained expression of target genes upon stimulation. These findings provide a direct link between maintenance of XCI and female-biased autoimmune manifestations and highlight altered XCI as a cause of autoimmunity.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adn6537","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T13:58:53Z","timestamp":1714744733000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":74,"title":["Altered X-chromosome inactivation predisposes to autoimmunity"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3082-342X","authenticated-orcid":true,"given":"Christophe","family":"Huret","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Epigenetics and Cell Fate, F-75013 Paris, 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