Decreased expression of IL-27 in moderate-to-severe psoriasis and its anti-inflammation role in imiquimod-induced psoriasis-like mouse model
Decreased expression of IL-27 in moderate-to-severe psoriasis and its anti-inflammation role in imiquimod-induced psoriasis-like mouse model
复制标题
中重度银屑病中IL-27表达的降低及其在咪喹莫特诱导的银屑病样小鼠模型中的抗炎作用
DOI：
10.1016/j.jdermsci.2016.11.011
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发表时间：
2017-02-01
影响因子：
4.6
通讯作者：
Shi, Yuling
中科院分区：
文献类型：
--
作者：
Chen, Wenjuan;Gong, Yu;Shi, Yuling
背景：银屑病是一种高发病率的T细胞介导的自身免疫性疾病，主要累及皮肤。白细胞介素（IL）-27是IL-6/IL-12细胞因子家族的新成员，其在不同T细胞亚群的分化和功能中起多方面的作用。以往的研究发现，IL-27通过促进辅助性T细胞（Th）I的分化促进银屑病的发病。目的：探讨IL-27在银屑病发病过程中的作用及其机制，特别是对Th 1和Th 17细胞的影响。研究方法：采用免疫组化和western blot方法检测正常皮肤和皮损组织中IL-27及其受体a（IL-27 Ra）的表达。ELISA法检测血清IL-27和IL-10水平。采用定量聚合酶链反应（PCR）分析皮肤组织和外周血单个核细胞（PBMC）中IL-27和IL-27受体（IL-27 R）mRNA的表达水平。为了探讨IL-27在体内的作用，我们采用咪喹莫特（IMQ）诱导的银屑病小鼠模型。用IL-27或其拮抗剂治疗小鼠，评估疾病严重程度，流式细胞术检测脾脏CD 4 + T细胞分泌细胞因子的情况，以及血清和皮损中IL-17和IFN-γ的表达水平。IL-27和IL-27 Ra的表达水平在中重度银屑病皮损中显著降低，沿着血清IL-27水平的一致降低。此外，IL-27重组蛋白皮下给药减轻了IMQ诱导的银屑病样皮肤病变的严重程度，而IL-27 p28拮抗剂加重了疾病的严重程度。进一步的分析显示，IL-27显著抑制了IL-17从CD 4 + T淋巴细胞的分泌。结论：IL-27可能通过抑制Th 17细胞的分化而在银屑病的发病机制中起保护作用。利用IL 27治疗银屑病的潜在治疗益处有待于未来的研究。(C)2016日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
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. (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.