Decreased expression of IL-27 in moderate-to-severe psoriasis and its anti-inflammation role in imiquimod-induced psoriasis-like mouse model

作者：Chen, Wenjuan; Gong, Yu; Zhang, Xilin; Tong, Yunlei; Wang, Xiuxiu; Fei, Chengwen; Xu, Hui; Yu, Qian; Wang, Yao; Shi, Yuling^*

来源：Journal of Dermatological Science, 2017, 85(2): 115-123.

DOI：10.1016/j.jdermsci.2016.11.011

• Psoriasis
• IL-27
• Th17
• Imiquimod

Background: Psoriasis is a high-incident T-cell-mediated autoimmune disease mainly affecting the skin. Interleukin (IL)-27 is a novel member of the IL-6/IL-12 cytokine family, which plays a versatile role in the differentiation and function of distinct T cell subsets. Previous studies uncovered that IL-27 promoted the onset of psoriasis through enhancing the differentiation of T helper (Th) I cells. However, the role of IL-27 in other psoriasis-related Th lineages, especially Th17 cells, remains elusive. @@@ Objects: The study aimed to investigate the role of IL-27 in the progression of psoriasis and its underlying mechanisms, particularly its influence on Thl and Th17. Methods: IL-27 and IL-27 receptor a (IL-27Ra) expressions in normal and lesional skin were determined by immunohistochemistry and western blot analysis. Serum levels of IL-27 and IL-10 were measured by ELISA. Expression levels of IL-27 and IL-27 receptor (IL-27R) mRNA in the skin tissue and peripheral blood mononuclear cells (PBMC) were assessed by quantitative polymerase chain reaction (PCR) analysis. To explore the function of IL-27 in vivo, we used imiquimod (IMQ)-induced psoriasis mouse model. We treated mice with IL-27 or its antagonist, evaluated disease severity and detected the cytokine secretion from splenic CD4+ T cells by flow cytometric analysis and the expression levels of IL-17 and IFN-gamma in serum and skin lesion. @@@ Results: The expression levels of IL-27 and IL-27Ra were significantly reduced in the moderate-to-severe psoriatic lesions, along with a consistent decrease in serum IL-27 levels, compared with those of healthy control subjects. Moreover, subcutaneous administration of IL-27 recombinant protein lessened severity of IMQ-induced psoriasis-like cutaneous lesions, whereas IL-27p28 antagonist exaggerated the disease severity. Further analysis revealed that IL-27 significantly repressed IL-17 secretion from CD4+ T lymphocytes. Also.administration of IL-27 decreased IL-17A level while IL-27p28 antagonist increased IL 17A level in serum and psoriasis-like lesion in the IMQ-treated mice. @@@ Conclusion: Our results suggest that IL-27 might predominantly play a protective role in the pathogenesis of psoriasis through abrogating Th17 differentiation. The potential therapeutic benefit of harnessing IL 27 in treating psoriasis awaits future investigation.

• 出版日期2017-2
• 单位中国人民解放军第二军医大学; 同济大学; 复旦大学