Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The res...Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The results presented demonstrate that Fyn deficient animals succumb to influenza infection ahead of the protective expansion of lung infiltrating T cells and viral clearance observed in wild-type hosts. Formal proof that Fyn-dependent IL-2 production mediates T cell expansion in vivo is provided using a model of T cell induced enteropathy. Specifically, Fyn deficient naive T cells do not induce colitis in SCID animals due to their lack of expansion, and Fyn re-expression rescues both IL-2 production and its capacity to support in vivo expansion leading to colitis. These results reconcile the obligatory role of Fyn in T cell activation and autocrine IL-2 supported growth;and underscore the mechanism through which its function is integrated with and regulated by Lck.展开更多
文摘Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The results presented demonstrate that Fyn deficient animals succumb to influenza infection ahead of the protective expansion of lung infiltrating T cells and viral clearance observed in wild-type hosts. Formal proof that Fyn-dependent IL-2 production mediates T cell expansion in vivo is provided using a model of T cell induced enteropathy. Specifically, Fyn deficient naive T cells do not induce colitis in SCID animals due to their lack of expansion, and Fyn re-expression rescues both IL-2 production and its capacity to support in vivo expansion leading to colitis. These results reconcile the obligatory role of Fyn in T cell activation and autocrine IL-2 supported growth;and underscore the mechanism through which its function is integrated with and regulated by Lck.
文摘目的本研究旨在探究差异表达基因(Differentially expressed genes,DEG),然后鉴别出急性心肌梗死(Acute myocardial infarction,AMI)关键基因,由此筛查出可用于这种研究早期诊断的心脏疾病潜在生物标记物。方法 AMI患者(GSE19339)的基因表达数据下载自基因表达汇编数据库。采用affy程序包预处理后,在samar程序包内通过微阵列显著性分析(Significance analysis of mycroarray,SAM)算法筛选DEG。然后使用DAVID(注释可视化和整合发现数据库软件,database for annotation visualization and integrated discovery software)在线工具进行DEG功能和通路富集分析。进而采用GENET-IC_ASSOCIATION_DB_DISEASE分析和blastp比对算法筛选出AMI的相关基因。最后,将这些新基因用于转录因子和蛋白-蛋白相互作用网络分析。结果在AMI患者与正常对照样本间共筛选出633个DEG,包括378个上调DEG和255个下调DEG。在AMI中发现了一种显著差异表达的新基因LCK(淋巴细胞特异性蛋白酪氨酸激酶,lymphocytespecific protein tyrosine kinase)。进一步分析显示LCK参与CXCL12(趋化因子(C-X-C基序)配体12,chemokine(C-X-Cmotif)ligand12)的表达调节,而LCK的表达则由不同的转录因子进行调节。结论这项研究中,我们对AMI的发病机制提出了新见解,并提出LCK是这种严重心脏疾病的一个引人注目的候选标记物。
