Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

Détails

ID Serval
serval:BIB_85ABECC56B2B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.
Périodique
Journal of immunology
Auteur(s)
Karampetsou M.P., Comte D., Kis-Toth K., Terhorst C., Kyttaris V.C., Tsokos G.C.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
15/06/2016
Peer-reviewed
Oui
Volume
196
Numéro
12
Pages
4915-4924
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype.

Mots-clé
Adult, Aged, Calcium/metabolism, Caspase 3/metabolism, Down-Regulation, Female, Humans, Immunoglobulin G/immunology, Interleukin-2/biosynthesis, Interleukin-2/immunology, Lupus Erythematosus, Systemic/blood, Lupus Erythematosus, Systemic/immunology, Lupus Erythematosus, Systemic/physiopathology, Lymphocyte Activation, Male, Middle Aged, Phosphorylation, Receptors, Antigen, T-Cell/immunology, Signal Transduction, Signaling Lymphocytic Activation Molecule Associated Protein/genetics, Signaling Lymphocytic Activation Molecule Associated Protein/metabolism, Signaling Lymphocytic Activation Molecule Family/genetics, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, Tyrosine/metabolism, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/07/2016 15:52
Dernière modification de la notice
20/08/2019 15:45
Données d'usage