Department of Cancer Immunology, The First Hospital of Jilin University, Changchun, China.
Department of Hematology, The First Hospital of Jilin University, Changchun, China.
Front Immunol. 2018 Jul 31;9:1787. doi: 10.3389/fimmu.2018.01787. eCollection 2018.
We recently discovered that dectin-1-activated dendritic cells (DCs) drive potent T helper (Th) 9 cell responses and antitumor immunity. However, the underlying mechanisms need to be further defined. The cytokine microenvironment is critical for Th cell differentiation. Here, we show that dectin-1 activation enhances interleukin (IL)-33 expression in DCs. We found that blocking IL-33/ST2 inhibits dectin-1-activated DC-induced Th9 cell differentiation. More importantly, the addition of IL-33 further promotes Th9 cell priming and antitumor efficacy induced by dectin-1-activated DCs. Mechanistically, in addition to the promotion of Th9 and Th1 cells, dectin-1-activated DCs combined with IL-33 abolish the activity of IL-33 in the induction of regulatory T cells. Furthermore, the combined treatment of dectin-1-activated DCs and IL-33 increases the frequencies of CD4 T cells by fostering their proliferation and inhibiting their exhaustive differentiation. Thus, our results demonstrate the important role of IL-33 in dectin-1-activated DC-induced Th9 cell differentiation and antitumor efficacy, and suggest that the combination of dectin-1-activated DCs and IL-33 may present a new effective modality of DC-based vaccines in tumor immunotherapy.
我们最近发现，Dectin-1 激活的树突状细胞（DC）可驱动强效的辅助性 T 细胞 9（Th9）细胞应答和抗肿瘤免疫。然而，其潜在机制尚需进一步明确。细胞因子微环境对于 Th 细胞分化至关重要。在此，我们发现 Dectin-1 激活可增强 DC 中的白细胞介素（IL）-33 表达。我们发现，阻断 IL-33/ST2 可抑制 Dectin-1 激活的 DC 诱导的 Th9 细胞分化。更重要的是，添加 IL-33 可进一步促进 Dectin-1 激活的 DC 诱导的 Th9 细胞的初始激活和抗肿瘤功效。在机制上，除了促进 Th9 和 Th1 细胞外，Dectin-1 激活的 DC 与 IL-33 联合可消除 IL-33 在诱导调节性 T 细胞中的活性。此外，Dectin-1 激活的 DC 和 IL-33 的联合治疗通过促进 CD4 T 细胞增殖和抑制其过度分化来增加 CD4 T 细胞的频率。因此，我们的结果表明 IL-33 在 Dectin-1 激活的 DC 诱导的 Th9 细胞分化和抗肿瘤功效中发挥重要作用，并提示 Dectin-1 激活的 DC 和 IL-33 的联合应用可能为肿瘤免疫治疗中的基于树突状细胞的疫苗提供一种新的有效方式。
