Wang Yuan, Xing Feiyue, Ye Siqi, Xiao Jia, Di Jingfang, Zeng Shan, Liu Jing
1] Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China [2] Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China.
Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
Sci Rep. 2015 Feb 4;5:8234. doi: 10.1038/srep08234.
Jagged-1 signaling has recently been reported to be involved in the Th17 cell differentiation. However, little is known about its mechanisms. Soluble Jagged-1 was used to activate the Jagged-1-Notch signaling to interfere with the IL-6 and TGF-β-induced Th17 cell skewing. Genes relevant to the autoimmunity or inflammation were screened for the first time in this system by qPCR array for the differential expressions. The 18 genes out of 84, including Clec7a, Il12b, Il12rb1, Il12rb2, Csf3, Il15, Il17a, Il17f, Il17rc, Il17rd, Il17re, Il23a, Myd88, Socs1, Stat4, Stat5a, Sykb and Tbx21, were downregulated, but only Cxcl2, Cxcl12 and Mmp3 were upregulated. The expressions of the genes, Rorγt, Il17a, Il17f, Il12rb1 and Il23a, induced by simultaneous IL-6 and TGF-β treatment were significantly suppressed by Jagged-1, followed by the reduction of RORγt, IL-17A, and IL-17F. Consistent with the attenuation of RORγt, and the reduced production and secretion of IL-17A and IL-17F in the cell supernatant and the in situ stained cells, the number of CD4(+)IL-17(+) cells was also diminished. It is concluded that the Jagged-1-Notch signaling can suppress the IL-6 and TGF-β treatment-induced Th17 cell skewing through the attenuation of RORγt and, hence by, the down-regulation of IL-17A, IL-17F, IL-23a, and IL-12rb1.
最近有报道称，Jagged-1信号通路参与了Th17细胞的分化。然而，其机制尚不清楚。使用可溶性Jagged-1激活Jagged-1-Notch信号通路，以干扰白细胞介素-6（IL-6）和转化生长因子-β（TGF-β）诱导的Th17细胞偏向分化。通过qPCR阵列首次在该系统中筛选与自身免疫或炎症相关的基因，以检测其差异表达。84个基因中的18个基因，包括Clec7a、Il12b、Il12rb1、Il12rb2、Csf3、Il15、Il17a、Il17f、Il17rc、Il17rd、Il17re、Il23a、Myd88、Socs1、Stat4、Stat5a、Sykb和Tbx21，表达下调，但只有Cxcl2、Cxcl12和Mmp3表达上调。Jagged-1显著抑制了IL-6和TGF-β同时处理诱导的Rorγt、Il17a、Il17f、Il12rb1和Il23a基因的表达，随后RORγt、IL-17A和IL-17F减少。与RORγt的减弱以及细胞上清液和原位染色细胞中IL-17A和IL-17F产生和分泌的减少一致，CD4(+)IL-17(+)细胞的数量也减少了。得出的结论是，Jagged-1-Notch信号通路可以通过减弱RORγt，从而下调IL-17A、IL-17F、IL-23a和IL-12rb1，来抑制IL-6和TGF-β处理诱导的Th17细胞偏向分化。
