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TLR7 and TLR8 are, respectively, encoded by adjacent X-linked genes. We previously established that\n                      <jats:italic>TLR7<\/jats:italic>\n                      evades X chromosome inactivation (XCI) in female immune cells. Whether\n                      <jats:italic>TLR8<\/jats:italic>\n                      also evades XCI, however, has not yet been explored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      In the current study, we used RNA fluorescence in situ hybridization (RNA FISH) to directly visualize, on a single-cell basis, primary transcripts of\n                      <jats:italic>TLR7<\/jats:italic>\n                      and\n                      <jats:italic>TLR8<\/jats:italic>\n                      relative to X chromosome territories in CD14\n                      <jats:sup>+<\/jats:sup>\n                      monocytes and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes from women, Klinefelter syndrome (KS) men, and euploid men. To assign X chromosome territories in cells lacking robust expression of a\u00a0XIST compartment, we designed probes specific for X-linked genes that do not escape XCI and therefore robustly label the active X chromosome. We also assessed whether XCI escape of\n                      <jats:italic>TLR8<\/jats:italic>\n                      was associated with sexual dimorphism in TLR8 protein expression by western blot and flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Using RNA FISH, we show that\n                      <jats:italic>TLR8<\/jats:italic>\n                      , like\n                      <jats:italic>TLR7<\/jats:italic>\n                      , evades XCI in immune cells, and that cells harboring\u00a0simultaneously\n                      <jats:italic>TLR7<\/jats:italic>\n                      and\n                      <jats:italic>TLR8<\/jats:italic>\n                      transcript foci are more frequent in women and KS men than in euploid men, resulting in a sevenfold difference in frequency.\u00a0This\u00a0transcriptional bias was again observable when comparing the single X of XY males with the active X of cells from females or KS males. Interestingly, TLR8 protein expression was significantly higher in female mononuclear blood cells, including all monocyte subsets, than in male cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TLR8<\/jats:italic>\n                      , mirroring\n                      <jats:italic>TLR7<\/jats:italic>\n                      , escapes XCI in human monocytes and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Co-dependent transcription from the active X chromosome and escape from XCI could both contribute to higher TLR8 protein abundance in female cells, which may have implications for the response to viruses and bacteria, and the risk of developing inflammatory and autoimmune diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-023-00544-5","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T05:02:07Z","timestamp":1695013327000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-4489","authenticated-orcid":false,"given":"Ali","family":"Youness","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-7851","authenticated-orcid":false,"given":"Claire","family":"Cenac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1160-8543","authenticated-orcid":false,"given":"Berenice","family":"Faz-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-448X","authenticated-orcid":false,"given":"Solange","family":"Grunenwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-0850","authenticated-orcid":false,"given":"Franck J.","family":"Barrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-2890","authenticated-orcid":false,"given":"Julie","family":"Chaumeil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-8870","authenticated-orcid":false,"given":"Jos\u00e9 Enrique","family":"Mej\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4499-3270","authenticated-orcid":false,"given":"Jean-Charles","family":"Gu\u00e9ry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"issue":"11","key":"544_CR1","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1172\/JCI26032","volume":"115","author":"A-S Beignon","year":"2005","unstructured":"Beignon A-S, McKenna K, Skoberne M, Manches O, DaSilva I, Kavanagh DG, et al. 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