Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
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DOI：
10.4049/jimmunol.1102797
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发表时间：
2012-01-15
期刊：
影响因子：
--
通讯作者：
Elkon KB
中科院分区：
文献类型：
--
作者：
Santer DM;Wiedeman AE;Teal TH;Ghosh P;Elkon KB
免疫复合物（ic）在引起系统性红斑狼疮（SLE）炎症中起关键作用3。然而，目前尚不清楚狼疮ic刺激的主要血细胞类型和炎症相关基因程序是什么。为了解决这些问题，我们将正常的人外周血单核细胞（PBMCs）或CD14+分离的单核细胞暴露于存在或不存在C1q的SLE ic中，并进行微阵列分析和其他细胞激活测试。通过芯片分析，我们确定了由SLE ic调节的基因和途径，这些基因和途径既依赖于I型IFN，也独立于I型IFN。我们还发现，含有ic的C1q显著降低了大多数ifn应答基因的表达，并影响了SLE ic诱导的多种其他基因的表达。令人惊讶的是，IC激活分离的CD14+单核细胞并没有上调CD40和CD86，只是适度刺激炎症基因表达。然而，当单核细胞亚群被纯化并单独分析时，低丰度的CD14dim（“巡逻”）亚群对ic更敏感。这些观察结果证明了浆细胞样树突状细胞（pDCs）、CD14dim单核细胞和C1q作为ic炎症特性的关键调节因子的重要性，并确定了它们起作用的许多途径。
Immune complexes (ICs) play a pivotal role in causing inflammation in systemic lupus erythematosus (SLE)3. Yet, it remains unclear what the dominant blood cell type(s) and inflammation related gene programs stimulated by lupus ICs are. To address these questions, we exposed normal human peripheral blood mononuclear cells (PBMCs) or CD14+ isolated monocytes to SLE ICs in the presence or absence of C1q and performed microarray analysis and other tests for cell activation. By microarray analysis, we identified genes and pathways regulated by SLE ICs that are both type I IFN dependent and independent. We also found that C1q containing ICs markedly reduced expression of the majority of IFN-response genes and also influenced the expression of multiple other genes induced by SLE ICs. Surprisingly, IC activation of isolated CD14+ monocytes did not upregulate CD40 and CD86 and only modestly stimulated inflammatory gene expression. However, when monocyte subsets were purified and analyzed separately, the low abundance CD14dim (‘patrolling’) subpopulation was more responsive to ICs. These observations demonstrate the importance of plasmacytoid dendritic cells (pDCs), CD14dim monocytes and C1q as key regulators of inflammatory properties of ICs and identify many pathways through which they act.
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影响因子：
20.3
作者：
Boulland, Marie-Laure;Marquet, Jeanine;Castellano, Flavia
通讯作者：
Castellano, Flavia
影响因子：
4.4
作者：
Bovin, LF;Rieneck, K;Bendtzen, K
通讯作者：
Bendtzen, K
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
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
4.4
作者：
Hornung, V;Rothenfusser, S;Hartmann, G
通讯作者：
Hartmann, G