IL-27-induced modulation of autoimmunity and its therapeutic potential.
IL-27-induced modulation of autoimmunity and its therapeutic potential.
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DOI：
10.1016/j.autrev.2015.08.001
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发表时间：
2015-12
影响因子：
13.6
通讯作者：
Moudgil KD
中科院分区：
文献类型：
--
作者：
Meka RR;Venkatesha SH;Dudics S;Acharya B;Moudgil KD
白细胞介素-27 （IL-27）是IL-12家族的新成员。它由活化的抗原提呈细胞产生，在调节CD4+ T细胞分化和免疫应答中起重要作用。IL-27激活多种信号级联，包括JAK-STAT和p38 MAPK通路。多项研究表明，IL-27促进Th1和Tr1的分化，但抑制Th2、Th17和Treg细胞。然而，一些研究表明，对某些T细胞亚群，如Treg，有相反的作用。IL-27在不同的自身免疫性疾病中具有促炎和抗炎活性。在这里，我们讨论了IL-27在类风湿关节炎、多发性硬化症、结肠炎、狼疮、牛皮癣、1型糖尿病和葡萄膜炎中的作用。这些信息大多来自于这些自身免疫性疾病的实验模型。IL-27在炎症和自身免疫中的双重作用的机制基础尚未完全确定。一般来说，IL-27的促炎/抗炎活性受潜在的免疫效应途径、疾病的阶段、抗调节细胞因子/T细胞亚群的存在或缺失以及所研究的组织/细胞类型的影响。尽管在各种自身免疫性疾病中有一系列的结果，但在这类疾病中观察到的主要是IL-27的抗炎和免疫调节作用。因此，IL-27代表了一种新的、有希望的治疗自身免疫性疾病的靶点/药物。
Interleukin-27 (IL-27) is a new member of the IL-12 family. It is produced by activated antigen-presenting cells and plays an important role in the regulation of CD4+ T cell differentiation and immune response. IL-27 activates multiple signaling cascades, including the JAK-STAT and p38 MAPK pathways. Several studies have revealed that IL-27 promotes the differentiation of Th1 and Tr1, but inhibits Th2, Th17, and Treg cells. However, a few studies have shown an opposite effect on certain T cell subsets, such as Treg. IL-27 displays both pro- and anti- inflammatory activities in different autoimmune diseases. Here, we have discussed the role of IL-27 in rheumatoid arthritis, multiple sclerosis, colitis, lupus, psoriasis, type 1 diabetes, and uveitis. Most of this information is derived from experimental models of these autoimmune diseases. The mechanistic basis of the dual role of IL-27 in inflammation and autoimmunity is still not fully defined. In general, the pro-/ anti- inflammatory activity of IL-27 is influenced by the underlying immune effector pathways, the phase of the disease, the presence or absence of counter-regulatory cytokines/T cell subsets, and the tissue/cell type under study. Despite a spectrum of outcomes in various autoimmune diseases, mostly anti-inflammatory and immunomodulatory effects of IL-27 have been observed in this category of diseases. Accordingly, IL-27 represents a novel, promising target/agent for the treatment of autoimmune diseases.