التفاصيل البيبلوغرافية
| العنوان: |
NBEAL2 deficiency in humans leads to low CTLA-4 expression in activated conventional T cells. |
| المؤلفون: |
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 |
| المصدر: |
Nature Communications; 6/22/2023, Vol. 14 Issue 1, p1-12, 12p |
| مصطلحات موضوعية: |
T cells, CYTOTOXIC T lymphocyte-associated molecule-4, REGULATORY T cells, RECESSIVE genes, MASS spectrometry |
| مستخلص: |
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. NBEAL2 loss of function mutations lead to grey platelet syndrome, a condition characterised by α-granule-deficient platelets and, in a proportion of cases, by autoimmunity. Here authors show that NBEAL2 physically interacts with CTLA-4 in human T cells, and NBEAL2 deficiency leads to reduced CTLA-4 surface expression in effector T cells, but not regulatory T cells, thus tipping the balance towards autoimmunity. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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