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Delage, Laure; Carbone, Francesco; Riller, Quentin; Zachayus, Jean-Luc; Kerbellec, Erwan; Buzy, Armelle; Stolzenberg, Marie-Claude; Luka, Marine; de Cevins, Camille; Kalouche, Georges; Favier, Rémi; Michel, Alizée; Meynier, Sonia; Corneau, Aurélien; Evrard, Caroline; Neveux, Nathalie; Roudières, Sébastien; Pérot, Brieuc P.; Fusaro, Mathieu; Lenoir, Christelle; Pellé, Olivier; Parisot, Mélanie; Bras, Marc; Héritier, Sébastien; [...]

NBEAL2 deficiency in humans leads to low CTLA-4 expression in activated conventional T cells

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  • Medientyp: E-Artikel
  • Titel: NBEAL2 deficiency in humans leads to low CTLA-4 expression in activated conventional T cells
  • Beteiligte: Delage, Laure; Carbone, Francesco; Riller, Quentin; Zachayus, Jean-Luc; Kerbellec, Erwan; Buzy, Armelle; Stolzenberg, Marie-Claude; Luka, Marine; de Cevins, Camille; Kalouche, Georges; Favier, Rémi; Michel, Alizée; Meynier, Sonia; Corneau, Aurélien; Evrard, Caroline; Neveux, Nathalie; Roudières, Sébastien; Pérot, Brieuc P.; Fusaro, Mathieu; Lenoir, Christelle; Pellé, Olivier; Parisot, Mélanie; Bras, Marc; Héritier, Sébastien; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-023-39295-7
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Loss of NBEAL2 function leads to grey platelet syndrome (GPS), a bleeding disorder characterized by macro-thrombocytopenia and α-granule-deficient platelets. A proportion of patients with GPS develop autoimmunity through an unknown mechanism, which might be related to the proteins NBEAL2 interacts with, specifically in immune cells. Here we show a comprehensive interactome of NBEAL2 in primary T cells, based on mass spectrometry identification of altogether 74 protein association partners. These include LRBA, a member of the same BEACH domain family as NBEAL2, recessive mutations of which cause autoimmunity and lymphocytic infiltration through defective CTLA-4 trafficking. Investigating the potential association between NBEAL2 and CTLA-4 signalling suggested by the mass spectrometry results, we confirm by co-immunoprecipitation that CTLA-4 and NBEAL2 interact with each other. Interestingly, NBEAL2 deficiency leads to low CTLA-4 expression in patient-derived effector T cells, while their regulatory T cells appear unaffected. Knocking-down NBEAL2 in healthy primary T cells recapitulates the low CTLA-4 expression observed in the T cells of GPS patients. Our results thus show that NBEAL2 is involved in the regulation of CTLA-4 expression in conventional T cells and provide a rationale for considering CTLA-4-immunoglobulin therapy in patients with GPS and autoimmune disease.</jats:p>
  • Zugangsstatus: Freier Zugang