MO_I_P: Molecular Sciences I. Posters
Panna Királyhidi1, Noémi Badari1, Zoltán Pós1, Tamás Németh2,3, Attila Mócsai2, Edit Buzás1, György Nagy1,3
1 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
2 Department of Physiology, Semmelweis University, Budapest
3 Department of Rheumatology and Clinical Immunology, Semmelweis University, Budapest
Introduction: in accordance with our previous data TNF α modulates T cell activation during inflammatory processes by regulating the CD3 ζ-chain expression via a Src-like adaptor protein (SLAP)-dependent mechanism. SLAP levels of the CD4+ T lymphocytes isolated from patients with RA were 2-fold higher than that of the healthy donors’, leading to the accelerated proteasomal degradation of CD3 ζ-chain. These data suggest the crucial role of SLAP in arthritis.
Aims: here we investigated the role of SLAP in collagen-induced arthritis (CIA).
Methods: SLAP knockout or heterozygous C57BL/6J mice were immunized with II. type collagen and complete Freund's adjuvant (CFA). Arthritis severity scores were monitored twice weekly for 2 months (1 limb score: 0=no swelling; 4=severe swelling), functional studies were also performed.
Results: The activity of arthritis (average total severity score) after the immunization was as follows (heterozygous vs. SLAP KO) at 5th, 6th and 8th weeks following immunization: 0 vs. 5.92 (P = 0.002); 0 vs. 8.75 (P = 0.002); 0 vs. 11.92 (P = 0.002) respectively.
Conclusion: SLAP deficiency completely protects from CIA.
Funding: UNKP-20-3 New National Excellence Program of the Ministry for Innovation and Technology; OTKA/NKFIHO NN 111023; OTKA/NKFIHN K 131479.
Reference: B. Érsek et al., J. Immunol., vol. 189, no. 4, pp. 1602–10, Aug. 2012.
Semmelweis University, Doctoral School of Molecular Medicine