Over-production of IFN-γ and IL-12 in AhR-null mice
Over-production of IFN-γ and IL-12 in AhR-null mice
复制标题
DOI：
10.1016/j.febslet.2005.10.023
复制
发表时间：
2005-11-21
期刊：
影响因子：
3.5
通讯作者：
Vega, L
中科院分区：
文献类型：
--
作者：
Rodríguez-Sosa, M;Elizondo, G;Vega, L
芳烃受体(AhR)是一种配体激活的转录因子，介导2，3，7，8-四氯二苯并-对二恶英等环境污染物的毒性。暴露于AhR激动剂会导致细胞和体液免疫反应的严重抑制，并危及宿主对传染病的抵抗力。因此，为了明确AhR在免疫应答中的作用，分别从卵蛋白(OVA)免疫的幼鼠和幼年小鼠分离脾细胞，并分别用OVA或有丝分裂原刀豆蛋白A(ConA)刺激。检测C57BL/6AhR-/-小鼠(AhR-/-)的T细胞增殖、CD19+、F4/80+、CD4+和CD8+T细胞增殖及细胞因子的产生，并与年龄匹配的野生型(AhR+/+)小鼠的免疫应答进行比较。在对OVA免疫的反应中，AhR-/-小鼠与AhR+/+动物相比，血清OVA特异性IgG2a、IgG1和IgG2b水平相似。然而，AhR-/-小鼠表现出脾肿大和B细胞增加。AhR-/-细胞比AhR+/+细胞产生更多的干扰素-γ和IL-12，但对细胞增殖和IL-4的分泌无明显影响。在ConA刺激下，AhR-/-细胞的IL-5水平明显低于AhR+/+细胞，而对IL-2的分泌无明显影响。在AhR-/-淋巴细胞中检测到高水平的干扰素-γmRNA，而在AhR-/-细胞中IL-4mRNA的水平与AhR+/+小鼠相似。提示AhR可能通过下调干扰素-γ和IL-12的表达，在免疫系统的正常发育和功能中发挥重要作用。
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates toxicity of environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. The exposure to AhR agonists results in profound suppression of cellular and humoral immune responses and compromises host to infectious disease. Therefore, to define the role of AhR in the immune response, spleen cells from ovalbumin (OVA)-immunized and naive mice were removed and stimulated in vitro with either OVA or mitogen concanavalin-A (Con A), respectively. Proliferation, CD19+, F4/80+, CD4+ and CD8+ T cells expansion and cytokines production were measured in C57BL/6AhR-/- mice (AhR-/-) and compared with immune response in similarly immunized age-matched wild type (AhR+/+) mice. In response to OVA immunization, AhR-/- mice had similar levels of serum OVA-specific IgG2a, IgG1, and IgG2b compared with AhR+/+ animals. However, AhR-/- mice showed splenomegalia and an increase in B cells. No changes were observed on proliferation and IL-4 secretion, although AhR-/- cells produced more IFN-gamma and IL-12 than AhR+/+ cells. Similar results were observed with Con A stimulation, a decrease on IL-5 and no change on IL-2 secretion were observed on AhR-/- cells compared with AhR+/+ cells in response to Con A stimulation. High levels of IFN-gamma mRNA were detected in AhR-/- lymphocytes, but IL-4 mRNA levels in AhR-/- cells were similar to those in AhR+/+ mice. These data suggest that AhR may play an important role in the normal development and function of immune system by down-regulating IFN-gamma and IL-12 expression.