Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases.
Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases.
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DOI：
10.1136/rmdopen-2015-000183
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发表时间：
2016
期刊：
影响因子：
6.2
通讯作者：
Smith KG
中科院分区：
文献类型：
--
作者：
Flint SM;Jovanovic V;Teo BW;Mak A;Thumboo J;McKinney EF;Lee JC;MacAry P;Kemeny DM;Jayne DR;Fong KY;Lyons PA;Smith KG
干扰素-1与系统性红斑狼疮(SLE)的发病机制有关，但大多数研究仅报道了干扰素-1对混合细胞群的影响。我们的目标是在纯化的白细胞群体中定义干扰素-1相关基因的模块，并将其作为详细比较分析的基础。从SLE患者、其他免疫介导性疾病患者和健康志愿者中分离纯化出CD4+和CD8+T细胞、单核细胞和中性粒细胞，并用基因芯片检测其基因表达。用加权基因共表达网络分析方法确定干扰素-1相关基因模块。分析了这些模块的组成和表达方式。在1288个干扰素-1相关基因中，有1150个基因是髓系亚群特有的，而T细胞特有的基因有11个。与T细胞相比，干扰素-1基因在髓系细胞亚群中表达更高。来自健康志愿者(HV)的一组中性粒细胞样本和与干扰素-1特征无关的条件显示，干扰素-1基因表达增加，而T细胞中干扰素-1相关基因的上调仅限于SLE。考虑到包括一些HV在内的中性粒细胞中干扰素-1基因的广泛上调，研究人员在报告基于全血样本的干扰素-1签名时应谨慎，不要将其解释为真正的干扰素-1介导的病理证据。相反，T细胞中干扰素-1相关基因的特异性上调可能是一个有用的生物标志物，也是干扰素-1升高促进SLE自身免疫的进一步机制。
Type 1 interferons (IFN-1) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-1 on mixed cell populations. We aimed to define modules of IFN-1-associated genes in purified leucocyte populations and use these as a basis for a detailed comparative analysis. CD4+ and CD8+ T cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers and gene expression then determined by microarray. Modules of IFN-1-associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed. 1150 of 1288 IFN-1-associated genes were specific to myeloid subsets, compared with 11 genes unique to T cells. IFN-1 genes were more highly expressed in myeloid subsets compared with T cells. A subset of neutrophil samples from healthy volunteers (HV) and conditions not classically associated with IFN-1 signatures displayed increased IFN-1 gene expression, whereas upregulation of IFN-1-associated genes in T cells was restricted to SLE. Given the broad upregulation of IFN-1 genes in neutrophils including in some HV, investigators reporting IFN-1 signatures on the basis of whole blood samples should be cautious about interpreting this as evidence of bona fide IFN-1-mediated pathology. Instead, specific upregulation of IFN-1-associated genes in T cells may be a useful biomarker and a further mechanism by which elevated IFN-1 contributes to autoimmunity in SLE.