Division of Immunobiology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
J Immunol. 2010 Nov 1;185(9):5111-9. doi: 10.4049/jimmunol.1001734. Epub 2010 Sep 24.
The generation of Th17 cells has to be tightly controlled during an immune response. In this study, we report an increase in a CD44(high)CD62L(-) Th17 subset in mice deficient for the protein tyrosine kinase Tec. CD44(high)CD62L(-) Tec(-/-) CD4(+) T cells produced enhanced IL-17 upon activation, showed increased expression levels of IL-23R and RORγt, and IL-23-mediated expansion of Tec(-/-) CD4(+) T cells led to an increased production of IL-17. Tec(-/-) mice immunized with heat-killed Streptococcus pneumoniae displayed increased IL-17 expression levels in the lung postinfection with S. pneumoniae, and this correlated with enhanced pneumococcal clearance and reduced lung inflammation compared with Tec(+/+) mice. Moreover, naive Tec(-/-) OT-II CD4(+) T cells produced higher levels of IL-17 when cultured with OVA peptide-loaded bone marrow-derived dendritic cells that have been previously activated with heat-killed S. pneumoniae. Taken together, our data indicated a critical role for Tec in T cell-intrinsic signaling pathways that regulate the in vivo generation of CD44(high)CD62L(-) effector/memory Th17 populations.
在免疫反应中，Th17 细胞的产生必须受到严格控制。在这项研究中，我们报告了 Tec 蛋白酪氨酸激酶缺失小鼠中 CD44(high)CD62L(-)Th17 亚群的增加。CD44(high)CD62L(-) Tec(-/-)CD4(+)T 细胞在激活后产生增强的 IL-17，表现出更高水平的 IL-23R 和 RORγt，并且 IL-23 介导的 Tec(-/-)CD4(+)T 细胞的扩增导致 IL-17 的产生增加。用热灭活肺炎链球菌免疫的 Tec(-/-)小鼠在感染 S. pneumoniae 后肺部的 IL-17 表达水平增加，与 Tec(+/+)小鼠相比，这与增强的肺炎球菌清除率和减少的肺部炎症相关。此外，与用热灭活 S. pneumoniae 预先激活的载有 OVA 肽的骨髓来源树突状细胞培养时，幼稚的 Tec(-/-)OT-II CD4(+)T 细胞产生更高水平的 IL-17。总之，我们的数据表明 Tec 在调节体内 CD44(high)CD62L(-)效应/记忆 Th17 群体产生的 T 细胞内信号通路中起着关键作用。
