| First Author | Kugyelka R | Year | 2019 |
| Journal | Cells | Volume | 8 |
| Issue | 5 | PubMed ID | 31137740 |
| Mgi Jnum | J:289320 | Mgi Id | MGI:6434994 |
| Doi | 10.3390/cells8050504 | Citation | Kugyelka R, et al. (2019) ZAP-70 Regulates Autoimmune Arthritis via Alterations in T Cell Activation and Apoptosis. Cells 8(5):504 |
| abstractText | 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. |
