Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis.
Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis.
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DOI：
10.1186/ar2933
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发表时间：
2010
影响因子：
4.9
通讯作者：
Joosten LA
中科院分区：
文献类型：
--
作者：
Plantinga TS;Fransen J;Takahashi N;Stienstra R;van Riel PL;van den Berg WB;Netea MG;Joosten LA
Dectin-1是一种由天然免疫系统表达的模式识别受体，是一种诱导Th17型获得性免疫反应的主要受体，已被证明可介导自身免疫。在这项研究中，我们研究了Dectin-1mRNA和蛋白的表达，以及最近发现的Dectin-1Y238X早期终止密码子多态性与类风湿关节炎(RA)易感性和严重程度的关系。检测类风湿关节炎(RA)、骨关节炎(OA)和非风湿性关节炎患者的滑膜组织标本中Dectin-1mRNA的表达。检测类风湿关节炎滑膜组织中Dectin-1蛋白的表达和定位。检测不同Dectin-1基因个体的巨噬细胞对Dectin-1刺激的细胞因子反应的差异。此外，262例RA患者的炎症和骨破坏的临床指标与Dectin-1Y238X基因多态性的存在相关。对滑膜组织活检中Dectin-1mRNA表达的评估显示，与OA和非风湿性关节炎患者的活检相比，类风湿关节炎标本中Dectin-1mRNA的表达增加。因此，在RA滑膜组织活检组织中，Dectin-1蛋白表达中等到高度，尤其是在巨噬细胞样细胞上。携带Dectin-1Y238X基因多态性的巨噬细胞在Dectin-1刺激下产生细胞因子的能力受到损害。然而，Dectin-1Y238X多态的存在与RA的易感性或疾病严重程度无关。虽然Dectin-1在RA患者滑膜组织中高表达，并在携带Dectin-1 Y238X多态的个体的巨噬细胞中观察到细胞因子的产生减少，但Dectin-1的一个功能等位基因缺失与RA的易感性或严重程度无关。
Dectin-1, a pattern recognition receptor expressed by the innate immune system, is known to be a major receptor inducing Th17-type adaptive immune responses that have been demonstrated to mediate autoimmunity. In this study, dectin-1 mRNA and protein expression, as well as the recently characterized DECTIN-1 Y238X early stop codon polymorphism, were studied in relation to rheumatoid arthritis (RA) susceptibility and severity. Dectin-1 mRNA expression was measured in synovial tissue specimens of RA, osteoarthritis (OA), and nonrheumatic patients. Dectin-1 protein expression and localization were assessed in RA synovial tissue specimens. Macrophages from individuals with different DECTIN-1 genotypes were examined for differences in cytokine responses on dectin-1 stimulation. Furthermore, clinical parameters of inflammation and bone destruction of 262 RA patients were correlated with the presence of the DECTIN-1 Y238X polymorphism. Evaluation of dectin-1 mRNA expression in synovial tissue biopsies revealed an increased expression in RA specimens, compared with biopsies from OA and nonrheumatic patients. Accordingly, dectin-1 protein expression in RA synovial tissue biopsies was moderate to high, especially on macrophage-like cells. Cytokine production capacity of macrophages bearing the DECTIN-1 Y238X polymorphism was demonstrated to be impaired on dectin-1 stimulation. However, the presence of the DECTIN-1 Y238X polymorphism was not associated with RA susceptibility or disease severity. Although expression of dectin-1 was high in synovial tissue of RA patients, and reduced cytokine production was observed in macrophages of individuals bearing the DECTIN-1 Y238X polymorphism, loss of one functional allele of DECTIN-1 is not associated with either susceptibility to or severity of RA.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
5.4
作者：
Osorio, Fabiola;LeibundGut-Landmann, Salome;Lochner, Matthias;Lahl, Katharina;Sparwasser, Tim;Eberl, Gerard;Reis e Sousa, Caetano
通讯作者：
Reis e Sousa, Caetano
影响因子：
20.3
作者：
Underhill, DM;Rossnagle, E;Simmons, RM
通讯作者：
Simmons, RM
影响因子：
30.5
作者：
Gringhuis, Sonja I.;den Dunnen, Jeroen;Geijtenbeek, Teunis B. H.
通讯作者：
Geijtenbeek, Teunis B. H.
影响因子：
3.7
作者：
Yordanov, M;Tchorbanov, A;Ivanovska, N
通讯作者：
Ivanovska, N