Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjogren's syndrome
Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjogren's syndrome
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DOI：
10.1073/pnas.0510837103
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发表时间：
2006-02-21
影响因子：
11.1
通讯作者：
Mariette, X
中科院分区：
文献类型：
--
作者：
Gottenberg, JE;Cagnard, N;Mariette, X
靶器官的基因表达分析可能有助于为自身免疫性疾病的发病机制提供新的见解。我们使用小唾液腺的整体基因表达谱来识别原发性干燥综合征（pSS）患者的基因表达模式，pSS是一种常见的原型系统性自身免疫性疾病。基因表达分析允许区分大多数pSS患者与对照。IFN途径中23个基因的表达，包括两个Toll样受体（TLR 8和TLR 9），在患者和对照组之间存在显著差异。此外，IFNI诱导的基因，BAFF和IFIN诱导的跨膜蛋白1的表达增加，也被证明在眼上皮细胞通过定量RT-PCR。体外激活实验表明，这些基因在pSS自身免疫的靶细胞唾液腺上皮细胞中被IFN有效地调节。IFN途径的激活使我们研究浆细胞样树突状细胞是否在唾液腺中被募集。这些IFN-产生细胞在所有pSS患者中通过免疫组化检测到，而在对照组中未观察到。总之，我们的研究结果支持pSS的先天性和适应性免疫系统之间的致病相互作用。IFN信号的持续存在可能与恶性循环有关，在恶性循环中，环境与遗传因素相互作用以驱动唾液TLR的刺激。
Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjogren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFNI-inducible genes, BAFF and IFIN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.