Dendritic Cell KLF2 Expression Regulates T Cell Activation and Proatherogenic Immune Responses.
Dendritic Cell KLF2 Expression Regulates T Cell Activation and Proatherogenic Immune Responses.
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DOI：
10.4049/jimmunol.1600206
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发表时间：
2016-12-15
期刊：
影响因子：
--
通讯作者：
Lichtman AH
中科院分区：
文献类型：
--
作者：
Alberts-Grill N;Engelbertsen D;Bu D;Foks A;Grabie N;Herter JM;Kuperwaser F;Chen T;Destefano G;Jarolim P;Lichtman AH
树突状细胞（Dendritic cells，DCs）在动脉粥样硬化等疾病中是先天性和适应性炎症的重要调节因子。然而，DC减轻或促进炎症发病机制的分子机制仅部分了解。先前的研究表明，转录因子KLF 2在调节参与动脉粥样硬化病变发展的各种细胞类型（包括内皮细胞、巨噬细胞和T细胞）的活化中具有重要的抗炎作用。我们使用泛DC，CD 11 c特异性cre-lox基因敲除小鼠模型来评估KLF 2在高胆固醇血症和动脉粥样硬化背景下DC激活，功能和炎症控制中的作用。我们发现KLF 2缺陷增强了DC表面共刺激分子CD 40和CD 86的表达，并促进了T细胞增殖和凋亡。与对照小鼠相比，将KLF 2缺陷型DC小鼠的骨髓移植到Ldlr−/−小鼠中会加重动脉粥样硬化，最可能的原因是血管炎症加剧，表现为病变内DC的存在增加，T细胞活化和细胞因子产生增强，以及动脉粥样硬化病变中细胞死亡增加。这些数据共同表明，KLF 2控制DC活化的程度，因此控制促动脉粥样硬化T细胞反应的强度。
Dendritic cells (DCs), have been implicated as important regulators of innate and adaptive inflammation in many diseases including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies have shown an important anti-inflammatory role for the transcription factor KLF2 in regulating activation of various cell types that participate in atherosclerotic lesion development, including endothelial cells, macrophages, and T cells. We used a pan-DC, CD11c-specific cre-lox gene knockout mouse model to assess the role of KLF2 in DC activation, function, and control of inflammation in the context of hypercholesterolemia and atherosclerosis. We found that KLF2 deficiency enhanced surface expression of costimulatory molecules CD40 and CD86 in DCs and promoted increased T cell proliferation and apoptosis. Transplant of bone marrow from mice with KLF2-deficient DCs into Ldlr−/− mice aggravated atherosclerosis compared to control mice, most likely due to heightened vascular inflammation evidenced by increased DC presence within lesions, enhanced T cell activation and cytokine production, and increased cell death in atherosclerotic lesions. Together these data indicate that KLF2 governs the degree of DC activation and hence the intensity of pro-atherogenic T cell responses.
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影响因子：
16.6
作者：
Herter JM;Grabie N;Cullere X;Azcutia V;Rosetti F;Bennett P;Herter-Sprie GS;Elyaman W;Luscinskas FW;Lichtman AH;Mayadas TN
通讯作者：
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作者：
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通讯作者：
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Kruppel 样因子 2 调节急性冠状动脉综合征患者的树突状细胞活化
影响因子：
--
作者：
Fang, Hongcheng;Lin, Jing;Li, Dazhu
通讯作者：
Li, Dazhu