The importance of sialoglycans for lymphocyte development and function

唾液酸聚糖对淋巴细胞发育和功能的重要性

• 批准号: 432178797
• 负责人: Professor Dr. Lars Nitschke
• 金额: --
• 依托单位: Department Biologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/432178797?language=en
• 关键词: importance; sialoglycans; lymphocyte; development; function

Sialoglycans are abundant glycan structures on the surface of lymphoyctes. They act as ligands for Siglec receptors or selectins, but also more general functions are described in the literature. This project has established mice with a B cell specific or T cell specific deletion of Cmas, a gene encoding for a crucial enzyme in sialoglycan synthesis. These mice with B cells, or respectively T cells, lacking sialoglycans showed a loss of the respective lymphocyte population in secondary lymphatic organs. It could be demonstrated that in both cases induction of apoptosis in these sialoglycan deficient lymphocytes is involved. Activated caspase 8 in Cmas- deficient B cells indicates activation of extrinsic apoptosis pathways triggered by the Fas-receptor. Poly-sialic and di-sialic acid expression on plasma cells was found. Di-sialic acid conjugates are generated by the enzyme ST8Sia6. Therefore, a new St8Sia6 deficient mouse was developed, to analyse the role of di-sialic acid conjugates further on these cell types. In the next funding period, the analysis of the mechanism of the B cell defect of the B cell specific Cmas deficient mouse will be finished. The role of Cmas in plasma cells and antibody responses will be examined, by using cre mice for a later deletion during B cell maturation. The T cell defect in T-cell specific Cmas deficient mice will be examined in detail. The role of di-sialic acid and 7,9 O-acetylation in plasma cell function and T cell function will be analyzed with the help of the newly established St8Sia6 deficient and with Casd1 conditional KO mice.

唾液酸聚糖是淋巴细胞表面上丰富的聚糖结构。它们充当Siglec受体或选择素的配体，而且在文献中描述了更一般的功能。该项目已经建立了具有Cmas的B细胞特异性或T细胞特异性缺失的小鼠，Cmas是编码唾液酸聚糖合成中的关键酶的基因。这些具有缺乏唾液酸聚糖的B细胞或T细胞的小鼠显示次级淋巴器官中相应淋巴细胞群的损失。可以证明，在这两种情况下，诱导这些唾液酸聚糖缺陷的淋巴细胞凋亡。Cmas缺陷型B细胞中激活的半胱天冬酶8表明Fas受体触发的外源性凋亡途径的激活。在浆细胞上发现多聚唾液酸和二唾液酸表达。二唾液酸缀合物由酶ST 8 Sia 6产生。因此，开发了一种新的St 8 Sia 6缺陷型小鼠，以进一步分析二唾液酸缀合物对这些细胞类型的作用。在下一个资助期，将完成B细胞特异性Cmas缺陷小鼠B细胞缺陷机制的分析。Cmas在浆细胞和抗体应答中的作用将通过使用cre小鼠在B细胞成熟期间的后期缺失来检查。将详细检查T细胞特异性Cmas缺陷小鼠中的T细胞缺陷。将在新建立的St 8 Sia 6缺陷型和Casd 1条件性KO小鼠的帮助下分析二唾液酸和7，9 O-乙酰化在浆细胞功能和T细胞功能中的作用。