Genetic deficiency of Syk protects mice from autoantibody-induced arthritis

Zoltán Jakus, Edina Simon, Bálint Balázs, Attila Mócsai

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76 Citations (Scopus)

Abstract

Objective. The Syk tyrosine kinase plays an important role in diverse functions in hematopoietic lineage cells. Although previous in vitro and pharmacologic analyses suggested Syk to be a possible player in the development of autoimmune arthritis, no in vivo genetic studies addressing that issue have yet been reported. The aim of the present study was to test whether genetic deficiency of Syk affects autoantibody-induced experimental arthritis in the K/BxN serum-transfer model. Methods. Syk-/- bone marrow chimeras carrying a Syk-deficient hematopoietic system were generated by transplanting Syk-/- fetal liver cells into lethally irradiated wild-type recipients. After complete repopulation of the hematopoietic compartment, autoantibody-mediated arthritis was induced by injection of arthritogenic K/BxN serum. Arthritis development was monitored by macroscopic and microscopic observation of the ankle joints, micro-computed tomography of bone morphology, as well as a joint function assay. Results. Genetic deficiency of Syk in the hematopoietic compartment completely blocked the development of all macroscopic and microscopic signs of arthritis. The Syk-/- mutation also prevented the appearance of periarticular bone erosions. Finally, Syk -/- bone marrow chimeras were completely protected from arthritis-induced loss of articular function. Conclusion. Our results indicate that Syk is critically involved in the development of all clinically relevant aspects of autoantibody-mediated K/BxN serum-transfer arthritis in experimental mice. These results provide the first in vivo genetic evidence of the role of Syk in the development of autoimmune arthritis.

Original languageEnglish
Pages (from-to)1899-1910
Number of pages12
JournalArthritis and rheumatism
Volume62
Issue number7
DOIs
Publication statusPublished - Jul 1 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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