Details

Autor(en) / 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
• Leverger, Guy
• Korganow, Anne-Sophie
• Picard, Capucine
• Latour, Sylvain
• Collet, Bénédicte
• Fischer, Alain
• Neven, Bénédicte
• Magérus, Aude
• Ménager, Mickaël
• Pasquier, Benoit
• Rieux-Laucat, Frédéric

Titel

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

Ist Teil von

• Nature communications, 2023-06, Vol.14 (1), p.3728-3728, Article 3728

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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.