| Summary: | 碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 105 === In the immune system, T cells play a critical role to clear abnormal cells and pathogens. However, this powerful weapon is also a double-edged sword. Without a strict control, it might start attacking our own tissues. During thymocyte development, there are two important checkpoints, positive selection and negative selection, to assure the mature T cells would be functional and non-harmful. Thymocytes undergoing these selection events constantly move to appropriate locations for their selection, and chemokines act as guidance signals during these migration events. While chemokines are important for inducing cell migration in the thymus, it is largely unknown if the chemokine gradient is constructed in soluble form, or immobilized by interaction with negatively charged molecules such as glycosaminoglycans.
Here, we determined the expression of negatively charged glycosaminoglycans. We found that Heparan sulfate, which is abundant in the thymus is predominantly expressed on thymus fibroblasts, while polysialic acid was most abundant on thymic dendritic cells. We also showed that several positively charged chemokines, such as CXCL12, CCL19 and CCL21 can bind to thymic fibroblasts in Heparan sulfate dependent manner. Finally, we found out that thymocytes migration was slowed down after enzymatic removal of heparan sulfate on thymic slices. Altogether, our results point to an important role of Heparan sulfate in regulating thymocytes motility by immobilizing chemokines.
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