Negative feedback regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions.
Negative feedback regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions.
复制标题
DOI：
10.1182/blood-2004-12-4738
复制
发表时间：
2005-09
期刊：
影响因子：
20.3
通讯作者：
K. Minami;Y. Yanagawa;K. Iwabuchi;N. Shinohara;T. Harabayashi;K. Nonomura;K. Onoé
中科院分区：
文献类型：
--
作者：
K. Minami;Y. Yanagawa;K. Iwabuchi;N. Shinohara;T. Harabayashi;K. Nonomura;K. Onoé
细胞外刺激调节树突状细胞（DC）激活自然杀伤T（NKT）细胞的能力还没有得到很好的理解。我们研究了辅助性T细胞1型（Th 1）/Th 2-细胞因子环境对小鼠NKT细胞介导的细胞因子产生的DC诱导的影响。用Th 1或Th 2细胞因子、白细胞介素（IL）-4或干扰素（IFN）-γ预处理髓样DC，导致NKT细胞在体外和体内产生的相互细胞因子的增强（例如，IL-4预处理导致Th 1细胞因子的增强）。因此，DC对Th 1或Th 2细胞因子的识别作为负反馈回路，通过NKT细胞功能维持Th 1/Th 2-细胞因子平衡。利用这些数据，我们在体内操纵细胞因子水平和先天性细胞溶解活性，以增加抗肿瘤反应。这是第一次描述一种新的调节系统，涉及DCs和NKT细胞的Th 1/Th 2细胞因子平衡。
The ability of extracellular stimuli to modulate dendritic cell (DC) activation of natural killer T (NKT) cells was not well understood. We investigated the effects of the T helper type 1 (Th1)/Th2-cytokine environment on DC induction of NKT cell-mediated cytokine production in mice. Pretreatment of myeloid DCs with Th1 or Th2 cytokines, interleukin (IL)-4 or interferon (IFN)-gamma, led to the enhanced production of reciprocal cytokines by NKT cells (eg, IL-4 pretreatment led to the enhanced production of Th1 cytokines) in vitro and in vivo. Thus, the recognition of Th1 or Th2 cytokines by DCs acts as a negative feedback loop to maintain Th1/Th2-cytokine balance via NKT cell functions. Using these data, we manipulated cytokine levels and innate cytolytic activity in vivo to increase an antitumor response. This is the first description of a novel regulation system governing Th1/Th2 cytokine balance involving DCs and NKT cells.