IL-17 Promotes Scar Formation by Inducing Macrophage Infiltration
IL-17 Promotes Scar Formation by Inducing Macrophage Infiltration
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IL-17 通过诱导巨噬细胞浸润促进疤痕形成
DOI：
10.1016/j.ajpath.2018.04.005
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发表时间：
2018
影响因子：
6
通讯作者：
Hu Dahai
中科院分区：
文献类型：
--
作者：
Zhang Julei;Qiao Qiao;Liu Mengdong;He Ting;Shi Jihong;Bai Xiaozhi;Zhang Yijie;Li Yan;Cai Weixia;Han Shichao;Guan Hao;Hu Dahai
影响深层真皮的创伤或烧伤通常会产生增生性瘢痕，这限制了患者的关节运动并产生美学问题。炎症被认为是主要的致病机制之一。我们发现，与正常皮肤相比，增生性瘢痕患者的瘢痕组织中IL-17增加。将重组小鼠IL-17皮下注射到接受全层切除手术的小鼠中，以研究IL-17在瘢痕形成中的作用。用IL-17刺激的小鼠表现出加重的纤维形成、延迟的伤口愈合和增加的炎症。此外，巨噬细胞浸润也增加。根据Transwell分析的结果，IL-17通过间接机制促进巨噬细胞浸润。用氯膦酸盐脂质体耗尽巨噬细胞后，IL-17的作用消失。单核细胞趋化蛋白（MCP）1、MCP 2和MCP 3（统称为MCP）的水平通过IL-17刺激而增加。Bindarit（MCP抑制剂）用于验证MCP的作用。此外，Ly 6C-低巨噬细胞负责小鼠中的伤口纤维化。在这项研究中，我们首次检测到IL-17水平的增加，并揭示IL-17通过MCP依赖性机制诱导特定亚型的巨噬细胞浸润以加重纤维化。因此，我们的研究结果提供了一个更好的理解瘢痕形成和新的策略，瘢痕预防。
Trauma or burn injuries that affect the deep dermis often produce a hypertrophic scar, which limits patients' joint movement and generates an aesthetic problem. Inflammation is believed to be one of the main pathogenic mechanisms. We found that IL-17 was increased in scar tissues from patients with hypertrophic scar compared with normal skin. Recombinant mouse IL-17 was subcutaneously injected into mice that underwent full-thickness excision surgery to investigate the role of IL-17 in scar formation. Mice stimulated with IL-17 showed aggravated fibrogenesis, delayed wound healing, and increased inflammation. In addition, macrophage infiltration was also increased. According to the results of the Transwell assay, IL-17 promoted macrophage infiltration through an indirect mechanism. After depleting macrophages with clodronate liposomes, the effect of IL-17 disappeared. Levels of monocyte chemotactic protein (MCP) 1, MCP2, and MCP3 (together referred to as MCPs) were increased by IL-17 stimulation. Bindarit (an inhibitor of MCPs) was used to verify the role of MCPs. In addition, the Ly6C-low macrophages were responsible for wound fibrogenesis in mice. In this study, we detected the increased levels of IL-17 for the first time and revealed that IL-17 induced the infiltration of a specific subtype of macrophages to aggravate fibrosis through an MCP-dependent mechanism. Thus, our results provide a better understanding of scar formation and new strategies for scar prevention.