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Open AccessArticle

ZAP-70 Regulates Autoimmune Arthritis via Alterations in T Cell Activation and Apoptosis

1
Department of Immunology and Biotechnology, Medical School, University of Pécs, H-7624 Pécs, Hungary
2
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, H-7624 Pécs, Hungary
3
Department of Radiology, Medical School, University of Pécs, H-7624 Pécs, Hungary
4
Molecular Pharmacology Research Group, Szentagothai Research Centre, University of Pécs, H-7624 Pécs, Hungary
5
Department of Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 504; https://doi.org/10.3390/cells8050504
Received: 18 March 2019 / Revised: 21 May 2019 / Accepted: 24 May 2019 / Published: 24 May 2019
(This article belongs to the Special Issue The Molecular and Cellular Basis for Rheumatoid Arthritis)
T cells play an essential role in the pathogenesis of both human rheumatoid arthritis (RA) and its murine models. A key molecule in T cell activation is ZAP-70, therefore we aimed to investigate the effects of partial ZAP-70 deficiency on the pathogenesis of recombinant human G1(rhG1)-induced arthritis (GIA), a well-established mouse model of RA. Arthritis was induced in BALB/c and ZAP-70+/− heterozygous mice. Disease progression was monitored using a scoring system and in vivo imaging, antigen-specific proliferation, cytokine and autoantibody production was measured and T cell apoptotic pathways were analyzed. ZAP-70+/− mice developed a less severe arthritis, as shown by both clinical picture and in vitro parameters (decreased T cell proliferation, cytokine and autoantibody production). The amount of cleaved Caspase-3 increased in arthritic ZAP-70+/− T cells, with no significant changes in cleaved Caspase-8 and -9 levels; although expression of Bim, Bcl-2 and Cytochrome C showed alterations. Tyrosine phosphorylation was less pronounced in arthritic ZAP-70+/− T cells and the amount of Cbl-b—a negative regulator of T cell activation—decreased as well. We hypothesize that the less severe disease seen in the partial absence of ZAP-70 might be caused by the decreased T cell activation accompanied by increased apoptosis. View Full-Text
Keywords: ZAP-70; T cells; apoptosis; autoimmune arthritis; intrinsic pathway; Cbl-b ZAP-70; T cells; apoptosis; autoimmune arthritis; intrinsic pathway; Cbl-b
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Kugyelka, R.; Prenek, L.; Olasz, K.; Kohl, Z.; Botz, B.; Glant, T.T.; Berki, T.; Boldizsár, F. ZAP-70 Regulates Autoimmune Arthritis via Alterations in T Cell Activation and Apoptosis. Cells 2019, 8, 504.

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