Systemic autoimmunity and defective Fas ligand secretion in the absence of the Wiskott-Aldrich syndrome protein
Détails
ID Serval
serval:BIB_4EC7D63AB835
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Systemic autoimmunity and defective Fas ligand secretion in the absence of the Wiskott-Aldrich syndrome protein
Périodique
Blood
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
2010
Volume
116
Numéro
5
Pages
740-7
Langue
anglais
Notes
Nikolov, Nikolay P
Shimizu, Masaki
Cleland, Sophia
Bailey, Daniel
Aoki, Joseph
Strom, Ted
Schwartzberg, Pamela L
Candotti, Fabio
Siegel, Richard M
eng
R21 AI079757/AI/NIAID NIH HHS/
Intramural NIH HHS/
Research Support, N.I.H., Intramural
Blood. 2010 Aug 5;116(5):740-7. doi: 10.1182/blood-2009-08-237560. Epub 2010 May 10.
Shimizu, Masaki
Cleland, Sophia
Bailey, Daniel
Aoki, Joseph
Strom, Ted
Schwartzberg, Pamela L
Candotti, Fabio
Siegel, Richard M
eng
R21 AI079757/AI/NIAID NIH HHS/
Intramural NIH HHS/
Research Support, N.I.H., Intramural
Blood. 2010 Aug 5;116(5):740-7. doi: 10.1182/blood-2009-08-237560. Epub 2010 May 10.
Résumé
Autoimmunity is a surprisingly common complication of primary immunodeficiencies, yet the molecular mechanisms underlying this clinical observation are not well understood. One widely known example is provided by Wiskott-Aldrich syndrome (WAS), an X-linked primary immunodeficiency disorder caused by mutations in the gene encoding the WAS protein (WASp) with a high incidence of autoimmunity in affected patients. WASp deficiency affects T-cell antigen receptor (TCR) signaling and T-cell cytokine production, but its role in TCR-induced apoptosis, one of the mechanisms of peripheral immunologic tolerance, has not been investigated. We find that WASp-deficient mice produce autoantibodies and develop proliferative glomerulonephritis with immune complex deposition as they age. We also find that CD4(+) T lymphocytes from WASp-deficient mice undergo reduced apoptosis after restimulation through the TCR. While Fas-induced cell death is normal, WASp deficiency affects TCR-induced secretion of Fas ligand (FasL) and other components of secretory granules by CD4(+) T cells. These results describe a novel role of WASp in regulating TCR-induced apoptosis and FasL secretion and suggest that WASp-deficient mice provide a good model for the study of autoimmune manifestations of WAS and the development of more specific therapies for these complications.
Mots-clé
Aging/immunology, Animals, Antibodies, Antinuclear/biosynthesis/blood, Apoptosis/*immunology, Autoimmune Diseases/*etiology, CD4-Positive T-Lymphocytes/immunology/pathology/*secretion, Crosses, Genetic, Cytoplasmic Granules/secretion, Fas Ligand Protein/*secretion, Glomerulonephritis, Membranoproliferative/*immunology, Immune Complex Diseases/immunology, Lymphocyte Activation, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Receptors, Antigen, T-Cell/*physiology, Wiskott-Aldrich Syndrome Protein/*deficiency/genetics/physiology
Pubmed
Open Access
Oui
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
20/08/2019 15:04