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A2.32 Experimental autoimmune arthritis in mice with cell-specific SYK-deletion
  1. T Németh,
  2. O Vilinovszki,
  3. K Szilveszter,
  4. A Mócsai
  1. Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary

Abstract

Background and objectives Autoimmune arthritides affect a significant proportion of the population and mean heavy burdens to patients. Despite of intensive research, the underlying pathological mechanisms are not completely understood yet. 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 crucial participants in experimental arthritis and Syk is an important component of their immunoreceptor (-like) signalling pathways among in vitro conditions. Here, we investigated whether Syk expression is required in these cell lines for the development of autoantibody-induced arthritis.

Materials and 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 analysed 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.

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