Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes.
Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes.
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DOI：
10.4049/jimmunol.1002615
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发表时间：
2011-01-15
期刊：
影响因子：
--
通讯作者：
Nikolajczyk BS
中科院分区：
文献类型：
--
作者：
Jagannathan-Bogdan M;McDonnell ME;Shin H;Rehman Q;Hasturk H;Apovian CM;Nikolajczyk BS
T细胞的促炎性（Th 17和Th 1）和抗炎性（调节性T细胞[Th 2]和Th 2）亚群之间的适当平衡对于维持体内平衡和避免炎性疾病至关重要。2型糖尿病（T2 D）是一种由免疫细胞功能变化促进的慢性炎症性疾病。最近的研究表明，T细胞是T2 D小鼠模型中重要的炎症介质。这些研究发现Th 17和Th 1亚群升高，Treg亚群降低，最终导致炎症和胰岛素抵抗。基于这些数据，我们检验了T2 D患者的T细胞偏向促炎亚群的假设。我们的数据显示，来自T2 D患者的血液增加了循环Th 17细胞，并提高了Th 17特征基因的激活。重要的是，T细胞需要与单核细胞一起培养以维持Th 17特征，并且来自T2 D患者的新鲜离体T细胞似乎准备用于IL-17产生。来自T2 D患者的T细胞也增加了IFN-γ的产生，但产生健康水平的IL-4。相反，T2 D患者的CD 4 + T细胞百分比降低。这些数据表明，T2 D患者中的T细胞自然偏向于促炎亚群，其可能通过升高的细胞因子产生促进T2 D中的慢性炎症。由于Th 17细胞和TcB之间的相互关系，需要谨慎对待针对重置这种平衡的潜在疗法。了解T2 D T细胞的独特方面对于预测此类治疗的结果至关重要。
An appropriate balance between proinflammatory (Th17 and Th1) and anti-inflammatory (regulatory T cells [Tregs] and Th2) subsets of T cells is critical to maintain homeostasis and avoid inflammatory disease. Type 2 diabetes (T2D) is a chronic inflammatory disease promoted by changes in immune cell function. Recent work indicates T cells are important mediators of inflammation in a mouse model of T2D. These studies identified an elevation in the Th17 and Th1 subsets with a decrease in the Treg subset, which culminates in inflammation and insulin resistance. Based on these data, we tested the hypothesis that T cells in T2D patients are skewed toward proinflammatory subsets. Our data show that blood from T2D patients has increased circulating Th17 cells and elevated activation of Th17 signature genes. Importantly, T cells required culture with monocytes to maintain Th17 signatures, and fresh ex vivo T cells from T2D patients appeared to be poised for IL-17 production. T cells from T2D patients also have increased production of IFN-γ, but produce healthy levels of IL-4. In contrast, T2D patients had decreased percentages of CD4+ Tregs. These data indicate that T cells in T2D patients are naturally skewed toward proinflammatory subsets that likely promote chronic inflammation in T2D through elevated cytokine production. Potential therapies targeted toward resetting this balance need to be approached with caution due to the reciprocal relationship between Th17 cells and Tregs. Understanding the unique aspects of T2D T cells is essential to predict outcomes of such treatments.
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