Weng Jianyu, Lai Peilong, Geng Suxia, Luo Chenwei, Wu Suijing, Ling Wei, Deng Chengxin, Huang Xin, Lu Zesheng, Du Xin
Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Clin Transplant. 2015 Jun;29(6):547-54. doi: 10.1111/ctr.12551. Epub 2015 May 5.
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 fibroblasts in 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.
皮肤损伤是慢性移植物抗宿主病（cGVHD）的特征性表现之一。当皮肤局部有效免疫转变为免疫失调反应时，皮肤损伤就会发生。Toll样受体4信号通路被认为是炎症和器官损伤的核心介质。在本研究中，我们发现皮肤型cGVHD患者外周血中的TLR4 mRNA与非GVHD患者及健康对照相比显著增加。此外，NF-κB表达、TLR4下游信号通路以及TLR4介导的细胞因子，包括IL-6和ICAM-1均上调。而且，ICAM-1广泛分布于皮肤型cGVHD患者的皮肤活检组织中。我们还发现脂多糖在体外可诱导人成纤维细胞中TLR4介导的NF-κB激活以及IL-6和ICAM-1分泌。因此，TLR4、NF-κB、IL-6和ICAM-1参与了皮肤型cGVHD中发生的炎症反应，表明TLR4信号通路可能是皮肤型cGVHD治疗的新靶点。
