Genetic deficiency of Syk protects mice from autoantibody-induced arthritis
Version of Record online: 3 MAR 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 7, pages 1899–1910, July 2010
How to Cite
Jakus, Z., Simon, E., Balázs, B. and Mócsai, A. (2010), Genetic deficiency of Syk protects mice from autoantibody-induced arthritis. Arthritis & Rheumatism, 62: 1899–1910. doi: 10.1002/art.27438
- Issue online: 29 JUN 2010
- Version of Record online: 3 MAR 2010
- Manuscript Accepted: 24 FEB 2010
- Manuscript Received: 17 NOV 2009
- Bolyai Research Fellowships from the Hungarian Academy of Sciences
- European Research Council (Starting Independent Investigator grant). Grant Number: 206283
- Hungarian Office for Research and Technology. Grant Number: Ányos Jedlik Program grant NKFP-A1-0069/2006
- International Senior Research Fellowships from the Wellcome Trust. Grant Numbers: 073976, 087782
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.
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.
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.
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.