CCN1 participates in the pathogenesis of Psoriasis by promoting IL-36γ expression
作者单位：Center for Clinical Laboratorythe First Affiliated Hospital of Soochow Hospital Shanghai Institute of Immunology & Department of Immunology and MicrobiologyShanghai Jiao Tong University School of Medicine
会议名称：《第十一届全国免疫学学术大会》
会议日期：2016年
学科分类：1002[医学-临床医学] 100206[医学-皮肤病与性病学] 10[医学]
关 键 词：Psoriasis CCN1 IL-36γ inflammation
摘 要：Objective: Psoriasis is a common chronic inflammatory skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Method: We have demonstrated that CCN1(also called Cyr61, which is short for cysteine-rich 61), an extra-cellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod(IMQ)- and IL-23-treated psoriasis-like ***: We found that the high expression of CCN1 is prior to that of IL-36γ during the process of imiquimod(IMQ)-and IL-23- treated psoriasis-like mice. Further, in Ha Ca T(human keratinocyte cell line) cells, CCN1, as an upstream stimulator, can promote IL-36γ expression, which was confirmed to be expressed in psoriasis lesions only as a biomarker. Finally, we observe that CCN1 stimulation activates the downstream phosphoinositide-3kinase/Akt/ NF- κB and ERK/AP1 signaling pathways through integrin receptor α6β***: CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix(ECM) protein. Our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent and upstream target for psoriasis treatment.