IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS
IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS
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DOI：
10.1111/j.1440-1711.2006.01419.x
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发表时间：
2006-04-01
影响因子：
4
通讯作者：
Thomas, R
中科院分区：
文献类型：
--
作者：
Peng, JC;Abu Bakar, S;Thomas, R
树突状细胞(DC)是细胞因子IL-12p70的主要产生者，通过其在Th1细胞的发育、CTL分化的共刺激和NK细胞的激活中发挥直接作用。相反，同样由DC产生的IL-10负向调节IL-12的产生。IL-12p70的产生在个体之间差异很大，编码IL-12p40(IL12B)的基因的几个多态性已经被发现影响感染性、自身免疫性和肿瘤疾病的易感性和严重程度。在这里，我们发现不仅IL12B基因的多态，而且IL10启动子的多态也会影响单核细胞来源的DC在内毒素刺激下分泌IL-12p70。虽然IL12B启动子纯合子容易产生更多的IL-12p70，但IL10高基因型的存在限制了这些个体的IL-12p70的产生。这些观察结果进一步提供了对IL-12p70调节的遗传控制，并强调了这种细胞因子产生的复杂性。他们还提出了可能影响DC免疫治疗结果的基因类型。
Dendritic cells (DC) are the main producers of the cytokine IL-12p70, through which they play a direct role in the development of IFN-gamma-secreting Th1 cells, costimulation of CTL differentiation and NK-cell activation. In contrast, IL-10, which is also produced by DC, negatively regulates IL-12 production. IL-12p70 production varies widely between individuals, and several polymorphisms in the gene encoding IL-12p40 (IL12B) have been identified that influence susceptibility and severity of infectious, autoimmune and neoplastic disease. Here we show that polymorphisms not only of IL12B, but also in the IL10 promoter, influence IL-12p70 secretion by monocyte-derived DC in response to LPS. Although IL12B promoter homozygotes were prone to making more IL-12p70, presence of the IL10 high genotype restricted IL-12p70 production in these individuals. These observations provide a further genetic control of IL-12p70 regulation and emphasize the complexity of production of this cytokine. They also suggest genotypes that might influence the outcome of DC immunotherapy.