Analysis of the function of lymphocyte adhesion molecules and its clinical significances in autoimmune diseases

b1整合素和配体的表达在类风湿关节炎（RA）的炎性病变中升高，crk相关底物淋巴细胞型（Cas-L）是一种对接蛋白，通过T细胞中β1整合素的参与，酪氨酸磷酸化程度很高。在本研究中，我们试图评估Cas-L在类风湿关节炎（RA）病理生理中的作用。我们分析了人类嗜t淋巴病毒I型（HTLV-I）转基因小鼠，因为它们发生类似于人类RA的多发性关节炎。本研究表明，有关节炎的转基因小鼠（Atg）脾脏细胞的迁移活性远高于无关节炎的转基因小鼠（Ntg）和同窝对照小鼠（Ct）。生化研究发现，Atg小鼠与Ntg和Ct小鼠相比，Cas-L蛋白及其自发酪氨酸磷酸化增加，这可能是由激活的fyn和lck引起的。免疫组化分析显示大量casl阳性淋巴细胞迁移到病变关节。最后，在人类风湿性关节炎中，casl阳性淋巴细胞已被证明浸润到炎性病变。以上结果强烈提示Cas-L可能在RA的病理生理中起重要作用。

It has been repeated that the expression of b1 integrins and ligands are elevated in the inflammatory lesions in rheumatoid arthritis (RA), Crk-associated substrate lymphocyte type (Cas-L) is a docking protein that is heavily tyrosine phosphorylated by the engagement of β1 integrins in T cells.In the present study, we attempted to evaluate the role of Cas-L in the pathophysiology of rheumatoid arthritis (RA). We analyzed human T-lymphotropic virus type I (HTLV-I) tax transgenic mice, since they develop polyarthritis resembling human RA. Here we show that migratory activity of spleen cells from tax transgenic mice with arthritis (Atg) was much higher than that of tax transgenic mice without arthritis (Ntg) and littermate control mice (Ct). Biochemical studies revealed that Cas-L protein and its spontaneous tyrosine phosphorylation were increased in Atg mice compared to Ntg and Ct mice, which might be caused by activated fyn and lck. Immunohistochemical analysis showed a large number of Cas-L positive lymphocytes migrating into the affected joints. Finally, in human RA, Cas-L positive lymphocytes have been shown to infiltrate to the inflammatory lesions. The above results strongly suggest that Cas-L appears to play an important role in the pathophysiology of RA.