Activation of the type I interferon pathway in primary Sjogren's syndrome
Activation of the type I interferon pathway in primary Sjogren's syndrome
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DOI：
10.1016/j.jaut.2010.06.012
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发表时间：
2010-11-01
影响因子：
12.8
通讯作者：
Crow, Mary K.
中科院分区：
文献类型：
--
作者：
Mavragani, Clio P.;Crow, Mary K.
干燥综合征（SS）是一种影响中年妇女的慢性自身免疫性全身性疾病，其特征在于唾液腺和泪腺的淋巴细胞浸润，导致眼干燥和口干燥。最近的进展已经揭示了激活的I型干扰素（IFN）途径在综合征的发病机制中的重要作用，如通过增加循环I型IFN活性和IFN“签名”在外周血单核细胞（PBMC）和小唾液腺（MSG）活检从这些患者。已发现参与IFN α途径的基因（如IRF 5和STAT 4）的多态性与疾病易感性相关。虽然先天性免疫应答的初始触发因素在SS中仍然难以捉摸，但初步证据支持不适当表达的内源性LINE-1（L1）逆转录因子作为SS中I型IFN活化的潜在触发因素的作用，可能通过Toll样受体（TLR）依赖或独立途径。胞苷脱氨酶的甲基化机制和APOBEC家族的蛋白质协同过表达，表明这些蛋白质可能有助于调节SS中不适当表达的L1内源性逆转录因子。考虑到IFN α在SS发病机制中的明显中心作用，阻断这种细胞因子可能是合理的治疗方法。在当前的综述中，我们总结了有关1型IFN激活潜在触发因素的当前证据，以及支持SS中I型IFN系统的遗传和表观遗传调节的数据。(C)2010爱思唯尔有限公司保留所有权利。
Sjogren's syndrome (SS), a chronic autoimmune systemic disease affecting middle aged women, is characterized by lymphocytic infiltration of the salivary and lachrymal glands resulting in dry eyes and dry mouth. Recent advances have revealed a major role for activation of the type I interferon (IFN) pathway in the pathogenesis of the syndrome, as evidenced by the increased circulating type I IFN activity and an IFN "signature" in peripheral blood mononuclear cells (PBMC) and minor salivary gland (MSG) biopsies from these patients. Polymorphisms in genes involved in the IFN alpha pathway, such as IRF5 and STAT4, have been found to be associated with disease susceptibility. While the initial triggers of the innate immune response in SS remain elusive, preliminary evidence supports the role of inappropriately expressed endogenous LINE-1 (L1) retroelements as potential triggers of type I IFN activation in SS, possibly through Toll-like receptor (TLR) dependent or independent pathways. Proteins of the methylation machinery and the APOBEC family of cytidine deaminases are coordinately overexpressed, suggesting that those proteins might contribute to regulation of the inappropriately expressed L1 endogenous retroelements in SS. Given the apparent central role of IFN alpha in the pathogenesis of SS, blockade of this cytokine may be a rational therapeutic approach. In the current review we summarize the current evidence regarding the potential triggers of type 1 IFN activation as well as the data supporting genetic and epigenetic regulation of the type I IFN system in SS. (C) 2010 Elsevier Ltd. All rights reserved.