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TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells.
Youness, Ali; Cenac, Claire; Faz-López, Berenice; Grunenwald, Solange; Barrat, Franck J; Chaumeil, Julie; Mejía, José Enrique; Guéry, Jean-Charles.
Afiliación
  • Youness A; Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), UMR 1291 INSERM, CNRS, Hôpital Purpan, Université de Toulouse, 31024, Toulouse, France.
  • Cenac C; Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), UMR 1291 INSERM, CNRS, Hôpital Purpan, Université de Toulouse, 31024, Toulouse, France.
  • Faz-López B; Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), UMR 1291 INSERM, CNRS, Hôpital Purpan, Université de Toulouse, 31024, Toulouse, France.
  • Grunenwald S; Service d'Endocrinologie, Maladies Métaboliques et Nutrition, Hôpital Larrey, Centre Hospitalier Universitaire (CHU) de Toulouse, 31059, Toulouse, France.
  • Barrat FJ; Hospital for Special Surgery, HSS Research Institute and David Z. Rosensweig Genomics Research Center, New York, NY, 10021, USA.
  • Chaumeil J; Department of Microbiology and Immunology, Weill Cornell Medical College of Cornell University, New York, NY, 10021, USA.
  • Mejía JE; INSERM, CNRS, Université Paris Cité, Institut Cochin, 75014, Paris, France.
  • Guéry JC; Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), UMR 1291 INSERM, CNRS, Hôpital Purpan, Université de Toulouse, 31024, Toulouse, France. jose-enrique.mejia@inserm.fr.
Biol Sex Differ ; 14(1): 60, 2023 09 18.
Article en En | MEDLINE | ID: mdl-37723501
Human endosomal Toll-like receptors TLR7 and TLR8, encoded by two adjacent X-linked genes, recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. We previously reported that TLR7 evades X chromosome inactivation (XCI) in female immune cells, correlating with enhanced functional properties in B cells harboring biallelic expression of this gene. Here, we conducted a comprehensive single-cell resolution analysis of the transcriptional regulation of both TLR7 and TLR8, in CD14+ monocytes and CD4+ T lymphocytes. We unequivocally demonstrated that TLR8, like TLR7, escapes XCI in immune cells from female and Klinefelter syndrome males. When we analyzed TLR7 and TLR8 transcripts together, cells from women and KS men exhibited higher frequencies of cells co-transcribing the two genes. Surprisingly, these differences were attributable not only to the ability of TLR7 and TLR8 to be expressed on the Xi, but also to the joint transcriptional behavior of the TLR7­TLR8 gene pair on the active X chromosome specifically. This contrasted with a striking pattern of mutually exclusive transcription on the single X of euploid men. Corroborating our RNA FISH results, we found higher TLR8 protein expression in female than in male leukocytes, including all monocyte subpopulations. In summary, our data suggest that sex-biased co-regulation of the Toll-like receptor locus and XCI escape of TLR8 contribute to the sexual dimorphism in TLR8 expression, which may have important consequences for the functional make-up of monocyte and T cell populations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Inactivación del Cromosoma X Límite: Female / Humans / Male Idioma: En Revista: Biol Sex Differ Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Inactivación del Cromosoma X Límite: Female / Humans / Male Idioma: En Revista: Biol Sex Differ Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido