{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:52:06Z","timestamp":1784872326101,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T00:00:00Z","timestamp":1560816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["Dnr 349-2006-237"],"award-info":[{"award-number":["Dnr 349-2006-237"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006310","name":"Medicinska Forskningsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The number of the X chromosome\u2013linked genes has been previously suggested to influence immune responses and the development of autoimmune diseases. In the present study, we aimed at evaluating the level of expression of CD40L (an X\u2010linked gene involved in adaptive immunity) and TLR7 (an X\u2010linked gene involved in innate immunity) in a variety of different karyotypes. Those included males, females and patients with X chromosome aneuploidy. Healthy females (46, XX; n\u00a0=\u00a010) and healthy males (46, XY; n\u00a0=\u00a010) were compared to females with Turner syndrome (TS) (45, X; n\u00a0=\u00a011) and males with Klinefelter syndrome (KS) (47, XXY; n\u00a0=\u00a05). Stimulation of peripheral blood mononuclear cells (PBMCs) with PMA and ionomycin resulted in higher percentage of CD3\u00a0+\u00a0CD40L+ T cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and higher level expression of CD40L in T cell (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) in female and KS patients compared with male and TS patients. TLR7\u2010mediated IFN\u2010alpha production by HLADR\u00a0+\u00a0CD3\u2212 CD19\u2212 cells was significantly upregulated in healthy women compared with healthy males, TS and KS patients (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). TLR7 agonist\u2010stimulated PBMCs from healthy females and KS patients expressed significantly higher levels of TLR7 mRNA than those from male and TS patients <jats:italic>(P<\/jats:italic>\u00a0&lt;\u00a00.05). The increased expression of the X\u2010linked genes TLR7 and CD40L in healthy females and KS patients suggests that the presence of two X chromosomes plays a major role in enhancing both innate and adaptive immune responses. These results may contribute to the explanation of sex\u2010based differences in immune biology and the sex bias in predisposition to autoimmune diseases.<\/jats:p>","DOI":"10.1111\/sji.12776","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T07:40:15Z","timestamp":1557387615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Copy number of the X<i>\u2010<\/i>linked genes TLR7 and CD40L influences innate and adaptive immune responses"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3694-1211","authenticated-orcid":false,"given":"Luis","family":"Sarmiento","sequence":"first","affiliation":[{"name":"Cellular Autoimmunity Unit, Department of Clinical Sciences Sk\u00e5ne University Hospital, Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sk\u00e5ne University Hospital Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Barchetta","sequence":"additional","affiliation":[{"name":"Cellular Autoimmunity Unit, Department of Clinical Sciences Sk\u00e5ne University Hospital, Lund University Malm\u00f6 Sweden"},{"name":"Department of Experimental Medicine Sapienza University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Giwercman","sequence":"additional","affiliation":[{"name":"Molecular Reproductive Medicine, Department of Translational Medicine Lund University, Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado M.","family":"Cilio","sequence":"additional","affiliation":[{"name":"Cellular Autoimmunity Unit, Department of Clinical Sciences Sk\u00e5ne University Hospital, Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/2141224a0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.09.110"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2007.05.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2009.03.005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2010.07.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/190372a0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1422906"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/349038a0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1098\/rstb.2011.0325","article-title":"Advances in understanding chromosome silencing by the long 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