Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production.
Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production.
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DOI：
10.1002/oby.21243
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Nikolajczyk BS
中科院分区：
文献类型：
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作者：
Ip B;Cilfone NA;Belkina AC;DeFuria J;Jagannathan-Bogdan M;Zhu M;Kuchibhatla R;McDonnell ME;Xiao Q;Kepler TB;Apovian CM;Lauffenburger DA;Nikolajczyk BS
T细胞炎症在肥胖相关的2型糖尿病（T2DM）中起关键作用。鉴定人类T细胞炎症的主要来源仍然是理解疾病发病机制的重要空白。我们假设来自循环T细胞的细胞因子谱可以识别定义t2dm相关炎症的T细胞亚群和T细胞因子。我们使用多重分析来量化αCD3/α cd28刺激的PBMCs或B细胞耗尽的PBMCs中T细胞相关细胞因子，这些PBMCs来自T2DM受试者或bmi匹配的对照组。我们对细胞因子测量进行多变量（主成分和偏最小二乘）分析。流式细胞术检测了多种免疫细胞亚群中存在/不存在中和T细胞因子的抗体的细胞内TNFα。T细胞因子在T2DM样本中普遍较高，但Th17细胞因子对于正确分类个体为T2DM尤为重要。多因素分析表明，B细胞支持T2DM患者的Th17炎症，而对照组不支持，而单核细胞支持Th17炎症，无论T2DM状态如何。偏最小二乘回归分析显示Th17和Th1细胞因子均影响%HbA1c。在各种T细胞亚群中，Th17细胞是炎症和高血糖的主要贡献者，并且在肥胖相关的T2DM中得到B细胞的独特支持。
T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. We hypothesized that cytokine profiles from circulating T cells identify T cell subsets and T cell cytokines that define T2DM-associated inflammation. We used multiplex analyses to quantify T cell-associated cytokines in αCD3/αCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM or BMI-matched controls. We subjected cytokine measurements to multivariate (principal component and partial least squares) analyses. Flow cytometry detected intracellular TNFα in multiple immune cells subsets in the presence/absence of antibodies that neutralize T cell cytokines. T cell cytokines were generally higher in T2DM samples, but Th17 cytokines are specifically important for classifying individuals correctly as T2DM. Multivariate analyses indicated that B cells support Th17 inflammation in T2DM but not control samples, while monocytes supported Th17 inflammation regardless of T2DM status. Partial least squares regression analysis indicated that both Th17 and Th1 cytokines impact %HbA1c. Among various T cell subsets, Th17 cells are major contributors to inflammation and hyperglycemia, and are uniquely supported by B cells in obesity-associated T2DM.