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肥胖会降低年轻人和老年人的B细胞反应。

Obesity decreases B cell responses in young and elderly individuals.

作者信息

Frasca Daniela, Ferracci Franco, Diaz Alain, Romero Maria, Lechner Suzanne, Blomberg Bonnie B

机构信息

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Department of Psychiatry, University of Miami Miller School of Medicine, Miami, Florida, USA.

出版信息

Obesity (Silver Spring). 2016 Mar;24(3):615-25. doi: 10.1002/oby.21383. Epub 2016 Feb 9.

Abstract

OBJECTIVE

To evaluate the effects of obesity-associated inflammation on influenza vaccine responses.

METHODS

In young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination were measured.

RESULTS

A decrease in in vivo vaccine responses, circulating switched memory, and transitional B cells and an increase in pro-inflammatory late/exhausted memory B cells were found. In vitro B cell function was measured by activation-induced cytidine deaminase and E47, markers of optimal antibody responses. Moreover, IL-6 production was increased, whereas IL-10 production was decreased in cultures of B cells from individuals with obesity. Markers of immune activation (TNF-α, TLR4, micro-RNAs) in unstimulated B cells were also found increased and were negatively correlated with B cell function. In order to reveal potential mechanisms, we stimulated B cells from lean individuals in vitro with leptin, the adipokine increased in obesity. Leptin increased phospho-STAT3, crucial for TNF-α production, and decreased phospho-AMPK, the energy sensing enzyme upstream of phospho-p38 MAPK and E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were similar to those in B cells from individuals with obesity.

CONCLUSIONS

These results demonstrate that leptin can be responsible for decreased B cell function in obesity.

摘要

目的

评估肥胖相关炎症对流感疫苗反应的影响。

方法

对年轻和老年个体(包括体重正常者和肥胖者)接种流感疫苗后的抗体反应进行检测。

结果

发现体内疫苗反应、循环转换记忆B细胞和过渡性B细胞减少,促炎性晚期/耗竭记忆B细胞增加。通过活化诱导胞苷脱氨酶和E47(最佳抗体反应的标志物)来检测体外B细胞功能。此外,肥胖个体B细胞培养物中白细胞介素-6的产生增加,而白细胞介素-10的产生减少。未受刺激的B细胞中免疫激活标志物(肿瘤坏死因子-α、Toll样受体4、微小RNA)也增加,且与B细胞功能呈负相关。为了揭示潜在机制,我们在体外用瘦素刺激体重正常个体的B细胞,瘦素是肥胖时增加的一种脂肪因子。瘦素增加了对肿瘤坏死因子-α产生至关重要的磷酸化信号转导和转录激活因子3,并降低了磷酸化腺苷酸活化蛋白激酶,磷酸化腺苷酸活化蛋白激酶是磷酸化p38丝裂原活化蛋白激酶和E47上游的能量感应酶。瘦素诱导的磷酸化信号转导和转录激活因子3及磷酸化腺苷酸活化蛋白激酶水平与肥胖个体B细胞中的水平相似。

结论

这些结果表明,瘦素可能是肥胖时B细胞功能降低的原因。

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