Analysis of partial ZAP-70 deficiency in a murine model of rheumatoid arthritis
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Tartalom: http://real.mtak.hu/27669/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Conference or Workshop Item
Cím:
Analysis of partial ZAP-70 deficiency in a murine model of rheumatoid arthritis
Létrehozó:
Kugyelka, Réka
Olasz, Katalin
Kohl, Zoltán
Sohn, Hee Seung
Tarjányi, Oktávia
Németh, Péter
Berki, Timea
Boldizsár, Ferenc
Dátum:
2015-09-06
Téma:
QP Physiology / élettan
R1 Medicine (General) / orvostudomány általában
Tartalmi leírás:
Recombinant human G1 (rhG1) induced arthritis (GIA) model resembles human rheumatoid arthritis (RA) both in immunological characteristics and clinical parameters. Immunization of BALB/c mice with rhG1 domain of human proteoglycan aggrecan induces arthritis. T cells are involved in the pathogenesis of arthritis; their activation is regulated by ZAP-70, a key molecule in T cell receptor signaling.
The aim of our study was to assess the effect of partial ZAP-70 deficiency on autoimmune arthritis in the GIA model.
Wild-type BALB/c (WT) and ZAP-70 heterozygous knockout (ZAP-70+/-) mice were immunized with rhG1 side-by-side. Surprisingly, partial ZAP-70 deficiency did not inhibit the development of GIA; moreover, the arthritis was more severe in ZAP-70+/- mice than in WT as assessed by the physical scoring system. Luminescence imaging confirmed the increased inflammatory activity in affected limbs of ZAP-70+/- mice compared to WT animals. There was a clear correlation between the results of the functional test (hanging time measurements) and the clinical scores. Alterations in the physical performance preceded the clinical onset of arthritis. Investigation of the T cell mediated immune response indicated decreased T cell proliferation and IL-4,-6 production accompanied by significant IL-17, IFN? and TNF? production measured from in vitro splenocyte cultures.
Contrary to our expectations partial deficiency of ZAP-70 did not ameliorate the severity of arthritis in GIA model, which may be due to alterations in T cell activation and apoptosis.
This work was funded by OTKA, K101493. and Bolyai Janos Reseach Scholarship of the Hungarian Academy of Sciences to FB.
Típus:
Conference or Workshop Item
NonPeerReviewed
Formátum:
text
Azonosító:
Kugyelka, Réka and Olasz, Katalin and Kohl, Zoltán and Sohn, Hee Seung and Tarjányi, Oktávia and Németh, Péter and Berki, Timea and Boldizsár, Ferenc (2015) Analysis of partial ZAP-70 deficiency in a murine model of rheumatoid arthritis. In: 4th European Congress of Immunology (ECI), 2015.09.06-09., Bécs, Ausztria.
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