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Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice.
Soudais, Claire; Schaus, Romane; Bachelet, Camille; Minet, Norbert; Mouasni, Sara; Garcin, Cécile; Souza, Caique Lopes; David, Pierre; Cousu, Clara; Asnagli, Hélène; Parker, Andrew; Palmquist-Gomes, Paul; Sepulveda, Fernando E; Storck, Sébastien; Meilhac, Sigolène M; Fischer, Alain; Martin, Emmanuel; Latour, Sylvain.
Afiliación
  • Soudais C; Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, Institut Imagine, Paris, France. claire.soudais@inserm.fr.
  • Schaus R; Université de Paris Cité, Paris, France. claire.soudais@inserm.fr.
  • Bachelet C; Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, Institut Imagine, Paris, France.
  • Minet N; Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, Institut Imagine, Paris, France.
  • Mouasni S; Université de Paris Cité, Paris, France.
  • Garcin C; Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, Institut Imagine, Paris, France.
  • Souza CL; Université de Paris Cité, Paris, France.
  • David P; Laboratory of Molecular Basis of Altered Immune Homeostasis Inserm UMR 1163, Institut Imagine, Paris, France.
  • Cousu C; Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, Institut Imagine, Paris, France.
  • Asnagli H; Université de Paris Cité, Paris, France.
  • Parker A; Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, Institut Imagine, Paris, France.
  • Palmquist-Gomes P; Université de Paris Cité, Paris, France.
  • Sepulveda FE; Transgenesis Platform, Laboratoire d'Expérimentation Animale et Transgenèse (LEAT), Institut Imagine-Structure Fédérative de Recherche Necker INSERM US24/CNRS, UMS3633, Paris, France.
  • Storck S; Université Paris Cité, CNRS UMR 8253, INSERM U1151, Institut Necker Enfants Malades, F-75015, Paris, France.
  • Meilhac SM; Step-Pharma, Technoparc du Pays-de-Gex, Saint-Genis-Pouilly, France.
  • Fischer A; Step-Pharma, Technoparc du Pays-de-Gex, Saint-Genis-Pouilly, France.
  • Martin E; Université de Paris Cité, Paris, France.
  • Latour S; Imagine - Institut Pasteur, Unit of Heart Morphogenesis, INSERM UMR1163, F-75015, Paris, France.
Nat Commun ; 15(1): 1982, 2024 Mar 04.
Article en En | MEDLINE | ID: mdl-38438357
ABSTRACT
De novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on the CTP synthetases, CTPS1 and -2. Partial CTPS1 deficiency in humans has previously been shown to lead to immunodeficiency, with impaired expansion of T and B cells. Here, we examine the effects of conditional and inducible inactivation of Ctps1 and/or Ctps2 on mouse embryonic development and immunity. We report that deletion of Ctps1, but not Ctps2, is embryonic-lethal. Tissue and cells with high proliferation and renewal rates, such as intestinal epithelium, erythroid and thymic lineages, activated B and T lymphocytes, and memory T cells strongly rely on CTPS1 for their maintenance and growth. However, both CTPS1 and CTPS2 are required for T cell proliferation following TCR stimulation. Deletion of Ctps1 in T cells or treatment with a CTPS1 inhibitor rescued Foxp3-deficient mice from fatal systemic autoimmunity and reduced the severity of experimental autoimmune encephalomyelitis. These findings support that CTPS1 may represent a target for immune suppression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoinmunidad / Desarrollo Embrionario Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoinmunidad / Desarrollo Embrionario Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido