{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:38:22Z","timestamp":1793403502216,"version":"4.5.0"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Glob. Women\u2019s Health"],"abstract":"<jats:p>Sex-based differences in immune function influence susceptibility to infections and predisposition to autoimmunity, with women showing both stronger immune responses and a higher burden of autoimmune and chronic inflammatory diseases. While sex hormones contribute to these differences, accumulating evidence highlights a central role for the X chromosome, which is enriched in immune-related genes and subject to complex regulatory mechanisms such as X-chromosome inactivation, skewing, escape from inactivation, and imprinting. Within this context, X chromosome\u2013encoded microRNAs (miRNAs) have emerged as key post-transcriptional regulators of immune homeostasis. The X chromosome harbors the highest density of miRNAs in the human genome, many of which target pathways involved in immune activation, tolerance, and tumorigenesis. Notably, some X-resident miRNAs escape X-chromosome inactivation, leading to female-biased expression that may enhance immune reactivity but also predispose to loss of tolerance and autoimmunity. In this minireview, we summarize current knowledge on X chromosome\u2013encoded miRNAs in immune regulation, discuss how their sex-biased expression patterns may contribute to female predominance in autoimmune diseases, and explore their potential utility as biomarkers and therapeutic targets for sex-aware precision medicine in inflammatory, autoimmune disorders and vaccine responses.<\/jats:p>","DOI":"10.3389\/fgwh.2026.1758961","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:24:15Z","timestamp":1771478655000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["X chromosome-encoded microRNAs in immune regulation: sex differences and clinical implications"],"prefix":"10.3389","volume":"7","author":[{"given":"Valeria","family":"Lodde","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Margarita","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Gorospe","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Campesi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari","place":["Sassari, 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