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OP0074 The Effect of Cell-Specific Syk-Deletion on Experimental Autoimmune Arthritis
  1. T. Nemeth,
  2. O. Vilinovszki,
  3. K. Szilveszter,
  4. A. Mocsai
  1. Department of Physiology, Semmelweis University, Budapest, Hungary

Abstract

Background Autoimmune arthritides mean heavy burdens both to patients and society, meaning that underlying pathological mechanisms are crucial to be investigated. Our workgroup previously published that the Syk tyrosine kinase is essential in experimental arthritis in mice. Probably, Syk expression in multiple cell lines is responsible for this effect. Neutrophils, platelets and mast cells are important players in experimental arthritis and Syk is a crucial component of their immunoreceptor(-like) signaling pathways among in vitro conditions.

Objectives Here, we investigated whether Syk expression is required in these cell lines for the development of autoantibody-induced arthritis in mice.

Methods Neutrophil-, platelet- and mast cell-specific Syk deletion was achieved by crossing MRP8, PF4 or Mcpt5 promoter-driven Cre recombinase transgenic (MRP8-Cre, PF4-Cre or Mcpt5-Cre) animals with Sykflox/flox mice (MRP8-Cre Sykflox/flox, PF4-Cre Sykflox/flox and Mcpt5-Cre Sykflox/flox, respectively). The efficacy and specificity of lineage-specific deletion was analyzed by Western-blot on neutrophil, platelet and mast cell lysates. Experimental arthritis was induced by a single intraperitoneal injection of K/BxN serum and was assessed by clinical scoring, ankle thickness measurements and by testing articular function.

Results In contrast to the wild type animals, neutrophils of the MRP8-Cre Sykflox/flox mice, platelets of the PF4-Cre Sykflox/flox mice and mast cells of Mcpt5-Cre Sykflox/flox mice did not express Syk, while their macrophages had normal levels of the protein. Interestingly, PF4-Cre Sykflox/flox and Mcpt5-Cre Sykflox/flox mice showed a similar disease phenomenon as their wild type controls. The changes of the clinical score, the ankle thickening and the articular dysfunction did not differ significantly in the three groups. Meanwhile, neutrophil-specific Syk deletion resulted in a severe attenuation of the disease.

Conclusions Our results indicate that – in contrast to the expectations – the presence of Syk in platelets and mast cells is not required for the development and progression of experimental arthritis, while Syk expression in neutrophils is indispensable for the pathogenesis.

References

  1. Jakus Z, Simon E, Balázs B, Mόcsai A. Genetic deficiency of Syk protects mice from autoantibody-induced arthritis. Arthritis Rheum 2010;62:1899-1910.

Acknowledgements T. Németh is a recipient of Bolyai Research Fellowship from the Hungarian Academy of Sciences.

Disclosure of Interest None declared

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