Investigation of the Role of Heparan Sulfate in Thymocyte Development

• Main Authors: Hsuan-Po Hsu, 徐璿博
• Other Authors: Ivan Dzhagalov
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/p8n6sz

碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 106 === T cells are one of the most important cell types in the immune system. They develop in the thymus through well-characterized series of steps. Migration is very important for thymocyte development because it allows them to access microenvironments supporting of positive and negative selections. Usually, thymocyte migration is guided by secreted molecules such as chemokines. For example, CCL19 and CCL21 are chemokines important for positively selecting thymocytes migrating from the cortex to the medulla. In the absence of chemokines, thymocytes cannot migrate to the medulla and be screened for auto-reactivity to tissue restricted antigens, which leads the mice to develop an autoimmune disease. While the role of chemokines in guiding thymocyte migration is clear, less is known about the form encountered by the cells, soluble or immobilized. Most chemokines (and many other secreted molecules) have positively charged sequences that can interact with negatively charged molecules such as the glycosaminoglycans (GAGs). We have found the most abundant GAG in the thymus is Heparan sulfate, and abundantly express on thymic fibroblasts, but not other cells in the thymus. Here, we demonstrate that the genetic model of Ext1-loxp x Pdgfra-cre (Ext1 cKO) mouse, resulted Ext1 conditional knockout on fibroblast. The Ext1 cKO mouse are embryonic lethal, so we performed fetal thymic organ culture (FTOC) to determine the role of HS in T cell development in thymus. The thymus from Ext1 cKO FTOC were smaller and had fewer cells. As a whole, our results indicate an important role of heparan sulfate in thymus development and T cell numbers.