The expression of"non-Th1"cytokines by"super Th1 cells"

我们之前证明了Th1细胞在对抗原、IL-2和IL-18的反应中获得了产生IL-13的能力，基于它们独特的功能，我们将这些活化的Th1细胞命名为“超级Th1细胞”。在这个项目中，我们发现当抗cd3、IL-18和IL-4共同刺激时，最初不表达于Th1细胞的gata结合蛋白3（Gata3）在表达t- bett的Th1细胞中被诱导，并且Gata3是超级Th1细胞中Il13基因表达所必需的。然而，Gata3诱导并不令人满意，额外的tcr信号是触发Gata3和表达t- bet的Th1细胞产生IL-13的先决条件。此外，我们发现超级Th1细胞同时产生IL-22，其数量与Th17细胞相当。此外，我们证实，当抗cd3、IL-2和IL-18刺激时，Th1细胞强烈增加Rorc基因的表达，该基因编码“th17主调控因子”Rorγt。这些发现表明Th1细胞有能力改变其细胞因子谱以响应外部刺激。

We previously demonstrated that Th1 cells gain the capacity to produce IL-13 in response to antigen, IL-2 and IL-18, and based on their unique function, we designated these activated Th1 cells as "super Th1 cells". In this project, we showed that when costimulated with anti-CD3, IL-18 and IL-4, the GATA-binding protein 3(Gata3), which is not originally expressed in Th1 cells, is induced in T-bet-expressing Th1 cells and that Gata3 is essentially required for Il13 gene expression in super Th1 cells. However, Gata3 induction is not satisfactory, and additional TCR-signaling is prerequisite for triggering IL-13 production by Gata3 plus T-bet-expressing Th1 cells. In addition, we revealed that super Th1 cells simultaneously produce IL-22, the amount of which is comparable to that of Th17 cells. Furthermore, we confirmed that when stimulated with anti-CD3, IL-2 and IL-18, Th1 cells strongly increased the expression of Rorc gene, which encodes Rorγt, "Th17-master regulator". These findings suggest that Th1 cells have the capacity to alter their cytokine profile in response to external stimuli.