Role of Toll-like receptor 4 signaling in cutaneous chronic graft-versus-host disease
Role of Toll-like receptor 4 signaling in cutaneous chronic graft-versus-host disease
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Toll 样受体 4 信号传导在皮肤慢性移植物抗宿主病中的作用
DOI：
10.1111/ctr.12551
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发表时间：
2015
影响因子：
2.1
通讯作者：
Du Xin
中科院分区：
文献类型：
--
作者：
Weng Jianyu;Lai Peilong;Geng Suxia;Luo Chenwei;Wu Suijing;Ling Wei;Deng Chengxin;Huang Xin;Lu Zesheng;Du Xin
皮肤损伤是慢性移植物抗宿主病（cGVHD）的特征性表现之一。当皮肤中的局部有效免疫改变为免疫异常反应时，发生皮肤损伤。Toll样受体4信号传导被认为是炎症和器官损伤的中心介质。在这项研究中，我们发现皮肤cGVHD患者外周血中的TLR 4 mRNA与非GVHD患者和健康对照相比显着增加。此外，NF-κB表达、TLR 4下游信号传导和TLR 4介导的细胞因子（包括IL-6和ICAM-1）上调。此外，ICAM-1广泛分布于皮肤cGVHD患者的皮肤活检组织中。我们还发现，LPS诱导TLR 4介导的NF-κB活化以及人成纤维细胞分泌IL-6和ICAM-1。因此，TLR 4、NF-κB、IL-6和ICAM-1促进了皮肤cGVHD中发生的炎症反应，表明TLR 4途径可能是皮肤cGVHD治疗的新靶点。
Cutaneous damage is one of the characterized manifestations in chronic graft‐versus‐host disease (cGVHD). When local effective immunity in the skin is altered to a dysimmune reaction, cutaneous injuries occur. Toll‐like receptor 4 signaling is regarded as a central mediator of inflammation and organ injury. In this study, we found that TLR4 mRNA in peripheral blood from patients with cutaneous cGVHD was markedly increased compared with that from non‐GVHD patients and healthy controls. In addition, NF‐κB expression, TLR4 downstream signaling, and TLR4‐mediated cytokines, including IL‐6 and ICAM‐1, were upregulated. Moreover, ICAM‐1 was widely distributed in skin biopsies from patients with cutaneous cGVHD. We also found that LPS induced TLR4‐mediated NF‐κB activation and IL‐6 and ICAM‐1 secretion in human fibroblastsin vitro. Thus, TLR4, NF‐κB, IL‐6, and ICAM‐1 contribute to the inflammatory response that occurs in cutaneous cGVHD, indicating the TLR4 pathway may be a novel target for cutaneous cGVHD therapy.