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Syk基因缺陷可保护小鼠免受自身抗体诱导的关节炎侵害。

Genetic deficiency of Syk protects mice from autoantibody-induced arthritis.

作者信息

Jakus Zoltán, Simon Edina, Balázs Bálint, Mócsai Attila

机构信息

Semmelweis University School of Medicine, Budapest, Hungary.

出版信息

Arthritis Rheum. 2010 Jul;62(7):1899-910. doi: 10.1002/art.27438.

DOI:10.1002/art.27438
PMID:20201079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2972644/
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.

摘要

目的

脾酪氨酸激酶（Syk）在造血谱系细胞的多种功能中发挥重要作用。尽管先前的体外和药理学分析表明Syk可能参与自身免疫性关节炎的发病过程，但尚未有针对该问题的体内遗传学研究报道。本研究的目的是检测Syk基因缺陷是否会影响K/BxN血清转移模型中自身抗体诱导的实验性关节炎。

方法

通过将Syk基因敲除（Syk-/-）的胎肝细胞移植到经致死剂量照射的野生型受体中，构建携带Syk缺陷造血系统的Syk-/-骨髓嵌合体。在造血系统完全重建后，通过注射致关节炎的K/BxN血清诱导自身抗体介导的关节炎。通过对踝关节的宏观和微观观察、骨形态的微计算机断层扫描以及关节功能测定来监测关节炎的发展。

结果

造血系统中Syk基因缺陷完全阻断了关节炎所有宏观和微观体征的发展。Syk-/-突变也阻止了关节周围骨侵蚀的出现。最后，Syk-/-骨髓嵌合体完全免受关节炎诱导的关节功能丧失。

结论

我们的结果表明，Syk在实验小鼠自身抗体介导的K/BxN血清转移关节炎的所有临床相关方面的发展中起关键作用。这些结果提供了Syk在自身免疫性关节炎发展中作用的首个体内遗传学证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/83a9a701d06e/art0062-1899-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/c0fd53ff44db/art0062-1899-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/1407b3fa800b/art0062-1899-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/1b0bf9106bb9/art0062-1899-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/a9f5434af266/art0062-1899-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/d6ff1f17d49d/art0062-1899-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/83a9a701d06e/art0062-1899-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/c0fd53ff44db/art0062-1899-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/1407b3fa800b/art0062-1899-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/1b0bf9106bb9/art0062-1899-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/a9f5434af266/art0062-1899-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/d6ff1f17d49d/art0062-1899-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/2972644/83a9a701d06e/art0062-1899-f6.jpg

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