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Altered X-chromosome inactivation predisposes to autoimmunity.
Huret, Christophe; Ferrayé, Léa; David, Antoine; Mohamed, Myriame; Valentin, Nicolas; Charlotte, Frédéric; Savignac, Magali; Goodhardt, Michele; Guéry, Jean-Charles; Rougeulle, Claire; Morey, Céline.
Afiliación
  • Huret C; Université Paris Cité, CNRS, Epigenetics and Cell Fate, F-75013 Paris, France.
  • Ferrayé L; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, University Paul Sabatier, Toulouse, France.
  • David A; Université Paris Cité, INSERM UMRS 976, Institut de Recherche Saint Louis, F-75010, Paris, France.
  • Mohamed M; Université Paris Cité, CNRS, Epigenetics and Cell Fate, F-75013 Paris, France.
  • Valentin N; Université Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, France.
  • Charlotte F; Sorbonne University, Department of Pathological Anatomy and Cytology, Hôpital Pitié-Salpêtrière Charles Foix, F-75013, Paris, France.
  • Savignac M; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, University Paul Sabatier, Toulouse, France.
  • Goodhardt M; Université Paris Cité, INSERM UMRS 976, Institut de Recherche Saint Louis, F-75010, Paris, France.
  • Guéry JC; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, University Paul Sabatier, Toulouse, France.
  • Rougeulle C; Université Paris Cité, CNRS, Epigenetics and Cell Fate, F-75013 Paris, France.
  • Morey C; Université Paris Cité, CNRS, Epigenetics and Cell Fate, F-75013 Paris, France.
Sci Adv ; 10(18): eadn6537, 2024 May 03.
Article en En | MEDLINE | ID: mdl-38701219
ABSTRACT
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 Xist, 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-nucleic 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoinmunidad / Receptor Toll-Like 7 / Inactivación del Cromosoma X / Macrófagos Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
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: Autoinmunidad / Receptor Toll-Like 7 / Inactivación del Cromosoma X / Macrófagos Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos