Nouri-Shirazi M, Kahlden C, Nishino P, Guinet E
Integrated Medical Science Department, Florida Atlantic University, Charles E. Schmidt College of Medicine, Boca Raton, FL, USA and.
Scand J Immunol. 2015 Feb;81(2):110-20. doi: 10.1111/sji.12254.
Dendritic cells (DCs) utilize polarizing signals to instruct the differentiation of T helper (Th) cells into Th1 and Th2 effector cells: antigen-specific 'signal 1', costimulatory 'signal 2' and polarizing cytokines 'signal 3'. Accumulating evidence suggests the involvement of an additional signal, the Notch signalling pathway. We reported that in response to Th1-promoting stimuli, both mouse and human DCs generated in the presence of the immune modulator nicotine (nicDCs) fail to support the development of effector memory Th1 cells. However, in response to Th2-promoting stimuli, these nicDCs preferentially support the differentiation of antigen-specific IL-4-producing Th2 effector cells. Here, we show that when compared to their control counterparts, immature mouse and human nicDCs display higher levels of the Notch ligands D1, D4 and J2 mRNA expression. In response to Th1- and Th2-promoting stimuli, mouse nicDCs display higher levels of the Notch ligands D1, D4 and J2, while human nicDCs show higher levels of D1, D4 and J1 mRNA expression. Furthermore, both stimulated mouse and human nicDCs express higher CD86 to CD80 ratio and produce lower amount of IL-12. Collectively, our data suggest that these changes in addition to an increase in Jagged expression correlate with the ability of nicDCs to modulate the Th1/Th2 balance in favour of Th2 generation.
树突状细胞（DCs）利用极化信号来指导辅助性T（Th）细胞分化为Th1和Th2效应细胞：抗原特异性的“信号1”、共刺激的“信号2”和极化细胞因子“信号3”。越来越多的证据表明，还存在一种额外的信号参与其中，即Notch信号通路。我们报道，在免疫调节剂尼古丁存在的情况下产生的小鼠和人类DCs（nicDCs），在受到促进Th1的刺激时，无法支持效应记忆性Th1细胞的发育。然而，在受到促进Th2的刺激时，这些nicDCs优先支持产生抗原特异性白细胞介素-4的Th2效应细胞的分化。在这里，我们表明，与对照DCs相比，未成熟的小鼠和人类nicDCs Notch配体D1、D4和J2的mRNA表达水平更高。在受到促进Th1和Th2的刺激时，小鼠nicDCs的Notch配体D1、D4和J2水平更高，而人类nicDCs的D1、D4和J1 mRNA表达水平更高。此外，受到刺激的小鼠和人类nicDCs均表达更高的CD86与CD80比值，并产生更少的白细胞介素-12。总体而言，我们的数据表明，除了锯齿状蛋白表达增加外，这些变化与nicDCs调节Th1/Th2平衡以利于Th2生成的能力相关。
