CD100-Plexin-B2 通过激活角质形成细胞中的 NF-κB 和炎性体促进银屑病炎症。
CD100-Plexin-B2 Promotes the Inflammation in Psoriasis by Activating NF-κB and the Inflammasome in Keratinocytes.
机构信息
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
出版信息
J Invest Dermatol. 2018 Feb;138(2):375-383. doi: 10.1016/j.jid.2017.09.005. Epub 2017 Sep 18.
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.
PlxnB2 及其配体 CD100 最初被鉴定为神经元发育过程中的轴突导向分子；然而，研究还表明 CD100- 聚蛋白参与各种免疫反应。在本研究中，我们发现银屑病患者皮损皮肤角质细胞上 PlxnB2 的表达特异性增加，而特应性皮炎则没有。银屑病患者血清中可溶性 CD100 和膜结合型 CD100 水平升高，分别在银屑病皮肤的角质细胞上。可溶性 CD100 通过与 PlxnB2 结合，促进角质细胞产生 CXCL-1、CCL-20、IL-1β 和 IL-18，并激活 NLRP3 炎性体。此外，CD100-PlxnB2 通过激活小 GTPase RhoA 和 Rac1 激活角质细胞中的 NF-κB 信号通路。我们的数据表明，CD100 和 PlxnB2 的协同作用通过激活 NF-κB 和 NLRP3 炎性体促进角质细胞的炎症反应，并参与银屑病的发病机制。CD100/PlxnB2 可能是银屑病的潜在治疗靶点。
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