Aspects of innate immunity in Sjögren's syndrome.
Aspects of innate immunity in Sjögren's syndrome.
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DOI：
10.1186/ar3318
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发表时间：
2011-05-27
影响因子：
4.9
通讯作者：
Witte T
中科院分区：
文献类型：
--
作者：
Low HZ;Witte T
以前，适应性免疫系统在Sjögren综合征发病机制中的主导作用被怀疑。然而，最近的进展已经揭示了I型IFN途径的主要作用，通过外周血单个核细胞和患者少量唾液腺活检中循环I型IFN活性的增加和IFN的“特征”来证明。导致IFN激活增加的基因IRF5和STAT4的多态性与疾病易感性相关。在Sjögren综合征的发病机制中，唾液腺上皮细胞的激活似乎是初始事件。一旦内在激活，它们表达共刺激和toll样受体（TLRs）以及MHC I类和II类分子，可以呈递自身抗原并产生促炎细胞因子。随后浆细胞样树突状细胞的激活诱导具有易感基因IRF5和STAT4风险等位基因的个体产生高水平的促炎细胞因子。在腺体内高浓度IFN的影响下，通过TLR结扎，上皮细胞产生b细胞活化因子，并结合自身抗原呈递唾液腺上皮细胞，刺激适应性免疫系统。鉴于ifn - α至少在Sjögren综合征发病机制的启动中起着核心作用，阻断这种细胞因子可能是一种合理的治疗方法。
Previously, a dominant role of the adaptive immune system in the pathogenesis of Sjögren's syndrome was suspected. Recent advances, however, have revealed a major role of the type I IFN pathway, documented by an increased circulating type I IFN activity and an IFN 'signature' in peripheral blood mononuclear cells and minor salivary gland biopsies from the patients. Polymorphisms in the genes IRF5 and STAT4 leading to increased IFN activation are associated with disease susceptibility. In the pathogenesis of Sjögren's syndrome, the activation of salivary gland epithelial cells appears to be the initial event. Once intrinsically activated, they express costimulatory and Toll-like receptors (TLRs) and MHC class I and II molecules, can present autoantigens and produce proinflammatory cytokines. The subsequent activation of plasmacytoid dendritic cells induces the production of high levels of proinflammatory cytokines in individuals with the risk alleles of the susceptibility genes IRF5 and STAT4. Under the influence of the high IFN concentration in the glands and through TLR ligation, B-cell activating factor is produced by epithelial cells and, together with autoantigen presentation on salivary gland epithelial cells, stimulates the adaptive immune system. In view of the central role of IFNalpha in at least the initiation of the pathogenesis of Sjögren's syndrome, blockade of this cytokine may be a rational therapeutic approach.
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影响因子：
27.4
作者：
Abelson AK;Delgado-Vega AM;Kozyrev SV;Sánchez E;Velázquez-Cruz R;Eriksson N;Wojcik J;Linga Reddy MV;Lima G;D'Alfonso S;Migliaresi S;Baca V;Orozco L;Witte T;Ortego-Centeno N;AADEA group;Abderrahim H;Pons-Estel BA;Gutiérrez C;Suárez A;González-Escribano MF;Martin J;Alarcón-Riquelme ME
通讯作者：
Alarcón-Riquelme ME
DOI：
10.1111/j.1600-0714.2008.00700.x
发表时间：
2009-01
期刊：
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
影响因子：
--
作者：
Deshmukh US;Nandula SR;Thimmalapura PR;Scindia YM;Bagavant H
通讯作者：
Bagavant H
影响因子：
--
作者：
Martinez, A.;Varade, J.;Urcelay, E.
通讯作者：
Urcelay, E.
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
影响因子：
4.7
作者：
Lee-Kirsch, Min Ae;Chowdhury, Dipanjan;Hubner, Norbert
通讯作者：
Hubner, Norbert