CD100-Plexin-B2 Promotes the Inflammation in Psoriasis by Activating NF-κB and the Inflammasome in Keratinocytes

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:138

Article

Zhang, Chen¹  Xiao, Chunying¹  Dang, Erle¹  Cao, Jiao¹  Zhu, Zhenlai¹  Fu, Meng¹  Yao, Xu^3,4  Liu, Yufeng¹  Jin, Boquan⁵  Wang, Gang¹  Li, Wei^1,2 

[1] Fourth Mil Med Univ, Xijing Hosp, Dept Dermatol, Xian 710032, Shaanxi, Peoples R China

[2] Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai, Peoples R China

[3] Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China

[4] Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China

[5] Fourth Mil Med Univ, Dept Immunol, Xian, Shaanxi, Peoples R China

DOI  :  10.1016/j.jid.2017.09.005

来源: Elsevier

【 摘 要 】

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-1 beta, and IL-18 by keratinocytes and activated the NLRP3 inflammasome. Moreover, CD100-PlxnB2 stimulated the NF-kappa B 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-kappa B and the NLRP3 inflammasome and participated in the pathogenesis of psoriasis. CD100/PlxnB2 might be a potential therapeutic target for psoriasis.

【 授权许可】

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