Mannan-binding lectin promotes keratinocyte to produce CXCL1 and enhances neutrophil infiltration at the early stages of psoriasis
Mannan-binding lectin promotes keratinocyte to produce CXCL1 and enhances neutrophil infiltration at the early stages of psoriasis
复制标题
甘露聚糖结合凝集素促进角质形成细胞产生CXCL1并增强银屑病早期阶段的中性粒细胞浸润
DOI：
10.1111/exd.13995
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发表时间：
2019
影响因子：
3.6
通讯作者：
Sun Ledong
中科院分区：
文献类型：
--
作者：
Zeng Jiaqi;Chen Xi;Lei Ke;Wang Di;Lin Lin;Wang Yajie;Li Yao;Liu Yunzhi;Zhang Liyun;Zuo Daming;Sun Ledong
牛皮癣是一种慢性、复发性炎症性皮肤病。大量的实验证据和治疗证据表明，先天免疫应答在银屑病的发病和发展中至关重要。甘露聚糖结合凝集素（MBL）是先天免疫系统的一种原型模式识别分子，在宿主防御某些感染中起着重要作用，似乎也是炎症的主要调节因子。在这项研究中，我们研究了MBL在实验性小鼠咪喹莫特（IMQ）诱导的银屑病过程中的功能。我们的数据表明，MBL缺陷（MBL-/-）小鼠表现出减弱的皮肤损伤，其特征是在IMQ诱导的银屑病样皮肤炎症的早期阶段，与野生型对照小鼠相比，红斑大大减少。MBL−/−小鼠皮肤炎症的减少与中性粒细胞浸润的减少有关。此外，我们已经确定MBL缺乏限制了IMQ刺激后皮肤角质形成细胞产生趋化因子CXCL 1，这可能是中性粒细胞皮肤募集受损的原因。此外，我们还提供了MBL蛋白在体外促进IMQ诱导的人角质形成细胞HaCaT中CXCL 1的表达和MAPK/NF-κB信号通路的激活的数据。总之，我们的研究揭示了MBL对皮肤角质形成细胞功能的意想不到的作用，从而为银屑病的发病机制提供了新的见解。
Psoriasis is a chronic, relapsing inflammatory skin disorder. Numerous experimental evidence and therapeutic evidence have shown that the innate immune response is critical for the pathogenesis and development of psoriasis. Mannan‐binding lectin (MBL), a prototypic pattern recognition molecule of the innate immune system, plays an essential role in the host defense against certain infections and also appears to be a major regulator of inflammation. In this study, we investigated the function of MBL on the course of experimental murine imiquimod (IMQ)‐induced psoriasis. Our data showed that MBL‐deficient (MBL−/−) mice exhibited attenuated skin damage characterized by greatly decreased erythema compared with wild‐type control mice during the early stages of IMQ‐induced psoriasis‐like skin inflammation. The reduced skin inflammation in MBL−/−mice was associated with the decreased infiltration of neutrophils. Furthermore, we have determined that MBL deficiency limited the chemokine CXCL1 production from skin keratinocytes upon IMQ stimulation, which might be responsible for the impaired skin recruitment of neutrophils. Additionally, we have provided the data that MBL protein promotes the IMQ‐induced expression of CXCL1 and activation of MAPK/NF‐κB signalling pathway in human keratinocyte HaCaT cells in vitro. In summary, our study revealed an unexpected role of MBL on keratinocyte function in skin, thus offering a new insight into the pathogenic mechanisms of psoriasis.