Pivotal role of CD103 in the development of psoriasiform dermatitis
Pivotal role of CD103 in the development of psoriasiform dermatitis
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DOI：
10.1038/s41598-020-65355-9
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发表时间：
2020-05-20
影响因子：
4.6
通讯作者：
Sato, Katsuaki
中科院分区：
文献类型：
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作者：
Fukui, Takehito;Fukaya, Tomohiro;Sato, Katsuaki
称为CD 103的整联蛋白α E结合整联蛋白β 7以形成完整的异源二聚体整联蛋白分子α E β 7。CD 103主要由肠、肺和皮肤的上皮组织内的淋巴细胞以及粘膜和真皮常规树突状细胞（cDC）的亚群表达。CD 103最初通过与肠上皮细胞、角质形成细胞和朗格汉斯细胞（LC）上表达的E-钙粘蛋白相互作用参与淋巴细胞与肠和皮肤中上皮的附着。然而，CD 103对皮肤免疫应答和炎症性皮肤病的发展的影响仍然难以捉摸。在这里，我们报道了CD 103通过控制cDCs的功能来调节银屑病样皮炎的发展。CD 103缺乏可加重银屑病样皮炎，伴有表皮过度增生和炎性白细胞浸润。此外，CD 103的缺乏不仅加速了银屑病病变中促炎细胞因子的产生，而且还促进了皮肤引流外周淋巴结（PLN）中产生白细胞介素（IL）-17的淋巴细胞的产生。在CD 103缺陷的情况下，位于PLN中的cDC在活化后增强细胞因子产生。因此，我们的发现揭示了CD 103在控制cDC调节银屑病样皮炎中皮肤炎症的功能中的关键作用。
The integrin alpha E known as CD103 binds integrin beta 7 to form the complete heterodimeric integrin molecule alpha E beta 7. CD103 is mainly expressed by lymphocytes within epithelial tissues of intestine, lung, and skin as well as subsets of mucosal and dermal conventional dendritic cells (cDCs). CD103 has been originally implicated in the attachment of lymphocytes to epithelium in the gut and skin through the interaction with E-cadherin expressed on intestinal epithelial cells, keratinocytes, and Langerhans cells (LCs). However, an impact of CD103 on the cutaneous immune responses and the development of inflammatory skin diseases remains elusive. Here, we report that CD103 regulates the development of psoriasiform dermatitis through the control of the function of cDCs. Deficiency in CD103 exacerbates psoriasiform dermatitis, accompanied by excessive epidermal hyperplasia and infiltration of inflammatory leukocytes. Furthermore, deficiency in CD103 not only accelerates the production of proinflammatory cytokines in psoriatic lesions but also promotes the generation of lymphocytes producing interleukin (IL)-17 in the skin-draining peripheral lymph nodes (PLNs). Under the deficiency in CD103, cDCs localized in PLNs enhance cytokine production following activation. Thus, our findings reveal a pivotal role for CD103 in the control of the function of cDCs to regulate cutaneous inflammation in psoriasiform dermatitis.