CCL17-CCR4轴在HIV感染者合并重型药疹的免疫机制研究

CCL17-CCR4轴是药疹发生的重要机制之一，CCL17水平与多型药疹严重程度相关，但普通人群重型药疹SJS／TEN与CCL17-CCR4轴无关。HIV感染者发生重型药疹病死率高，发病机制尚不清楚。我们前期研究发现HIV感染合并SJS／TEN患者血清CCL17水平升高，同时发现其CCR4受体表达上调。推测CCL17-CCR4轴在HIV感染者发生SJS/TEN中可能发挥重要作用。本项目通过检测临床实验组和对照组CCL17趋化因子及其CCR4受体表达，进行CCL17-CCR4轴相关炎症信号通路分子机制研究。使用CCR4受体阻断剂在Th2淋巴细胞模型中进一步验证；通过HIV-1病毒株刺激Th2淋巴细胞模型，探索HIV-1感染介导Th2淋巴细胞释放CCL17的机制。阐明HIV感染者发生SJS/TEN的免疫机制，为临床诊疗和开发CCL17-CCR4轴阻断药物提供依据。

CCL17-CCR4 axis is one of the important mechanisms of drug eruption. CCL17 level is related to the severity of drug eruption, but the SJS/TEN is not related to CCL17-CCR4 axis. The fatality rate of severe drug eruption in HIV-infected patients is high, but the pathogenesis is unclear. Our previous study found that HIV- infected patients with SJS/TEN show up-regulated expression in serum CCL17, and the expression of CCR4 receptor also increased. We speculate that CCL17-CCR4 axis may play a important role in HIV-infected patients with SJS /TEN. This project proposed by detecting CCL17 and CCR4 receptor expression between clinical experimental group and control group, aim to explore molecular mechanism of CCL17-CCR4 axis in inflammatory signaling pathways.To find out the mechanism of HIV-1 infection mediated Th2 cells to release CCL17 by stimulating Th2 cell model with HIV-1 strain. This study will clarify the pathogenesis of SJS/TEN in HIV-infected patients and provide basic data for the development of CCL17-CCR4 axis blocking drugs and clinical diagnosis and treatment .