CD100-Plexin-B2 Promotes the Inflammation in Psoriasis by Activating NF-kappaB and the Inflammasome in Keratinocytes.
CD100-Plexin-B2 Promotes the Inflammation in Psoriasis by Activating NF-kappaB and the Inflammasome in Keratinocytes.
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CD100-Plexin-B2 通过激活 NF-kappa B 和角质形成细胞中的炎症小体促进银屑病炎症
DOI：
10.1016/j.jid.2017.09.005
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Li Wei
中科院分区：
文献类型：
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作者：
Zhang Chen;Xiao Chunying;Dang Erle;Cao Jiao;Zhu Zhenlai;Fu Meng;Yao Xu;Liu Yufeng;Jin Boquan;Wang Gang;Li Wei
PlxnB2及其配体CD100最初被鉴定为在神经元发育期间起作用的轴突导向分子;然而，研究还表明CD100-丛蛋白参与各种免疫应答。在这项研究中，我们发现PlxnB2在角质形成细胞上的表达在银屑病患者的皮损中特异性增加，但在特应性皮炎中没有。可溶性CD 100和膜结合CD 100的水平升高银屑病患者的血清和银屑病皮肤的角质形成细胞，分别。通过与PlxnB2结合，可溶性CD100促进角质形成细胞产生CXCL-1、CCL-20、IL-1 β和IL-18，并激活NLRP 3炎性体。此外，CD 100-PlxnB2通过激活小G T β RhoA和Rac 1刺激角质形成细胞中的NF-κ B信号通路。结果表明，CD 100和PlxnB 2协同作用，通过激活NF-κ B和NLRP 3炎性小体，促进角质形成细胞的炎症反应，参与银屑病的发病机制。CD100/PlxnB2可能是银屑病治疗的潜在靶点。
PlxnB2 and its ligand, CD100, were originally identified as axon-guidance molecules that function during neuronal development; however, studies also showed that CD100-plexins participate in various immune responses. In this study, we found that the expression of PlxnB2 on keratinocytes was specifically increased in lesional skin of psoriasis patients but not atopic dermatitis. Levels of soluble CD100 and membrane-bound CD100 were elevated in sera of psoriasis patients and on keratinocytes of psoriatic skin, respectively. By binding to PlxnB2, soluble CD100 promoted the production of CXCL-1, CCL-20, IL-1β, and IL-18 by keratinocytes and activated the NLRP3 inflammasome. Moreover, CD100-PlxnB2 stimulated the NF-κB signaling pathway in keratinocytes through activation of small GTPase RhoA and Rac1. Our data showed that cooperation of CD100 and PlxnB2 promoted the inflammatory responses in keratinocytes by activating NF-κB and the NLRP3 inflammasome and participated in the pathogenesis of psoriasis. CD100/PlxnB2 might be a potential therapeutic target for psoriasis.