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肥胖状态下人类脂肪细胞与T淋巴细胞之间的相互作用:作为脂肪趋化因子的CCL20与作为脂肪生成调节因子的T淋巴细胞

Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators.

作者信息

Duffaut Carine, Zakaroff-Girard Alexia, Bourlier Virginie, Decaunes Pauline, Maumus Marie, Chiotasso Patrick, Sengenès Coralie, Lafontan Max, Galitzky Jean, Bouloumié Anne

机构信息

Institut National de la Santé et de la Recherche Médicale (INSERM), U858, Toulouse, France.

出版信息

Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1608-14. doi: 10.1161/ATVBAHA.109.192583. Epub 2009 Jul 30.

DOI:10.1161/ATVBAHA.109.192583
PMID:19644053
Abstract

OBJECTIVE

Adipose tissue (AT) plays a major role in the low-grade inflammatory state associated with obesity. The aim of the present study was to characterize the human AT lymphocytes (ATLs) and to analyze their interactions with adipocytes.

METHODS AND RESULTS

Human ATL subsets were characterized by flow cytometry in subcutaneous ATs from 92 individuals with body mass index (BMI) ranging from 19 to 43 kg/m(2) and in paired biopsies of subcutaneous and visceral AT from 45 class II/III obese patients. CD3(+) ATLs were composed of effector and memory CD4(+) helper and CD8(+) cytotoxic T cells. The number of ATLs correlated positively with BMI and was higher in visceral than subcutaneous AT. Mature adipocytes stimulated the migration of ATLs and released the chemokine CCL20, the receptor of which (CCR6) was expressed in ATLs. The expression of adipocyte CCL20 was positively correlated with BMI and increased in visceral compared to subcutaneous adipocytes. ATLs expressed inflammatory markers and released interferon gamma (IFN gamma). Progenitor and adipocyte treatment with ATL-conditioned media reduced the insulin-mediated upregulation of lipogenic enzymes, an effect involving IFN gamma.

CONCLUSIONS

Therefore, crosstalk occurs between adipocytes and lymphocytes within human AT involving T cell chemoattraction by adipocytes and modulation of lipogenesis by ATLs.

摘要

目的

脂肪组织(AT)在与肥胖相关的低度炎症状态中起主要作用。本研究的目的是对人AT淋巴细胞(ATL)进行表征,并分析它们与脂肪细胞的相互作用。

方法与结果

通过流式细胞术对92名体重指数(BMI)范围为19至43kg/m²的个体的皮下AT以及45名II/III级肥胖患者的皮下和内脏AT的配对活检组织中的人ATL亚群进行表征。CD3⁺ATL由效应和记忆CD4⁺辅助性T细胞和CD8⁺细胞毒性T细胞组成。ATL的数量与BMI呈正相关,且在内脏AT中高于皮下AT。成熟脂肪细胞刺激ATL的迁移并释放趋化因子CCL20,其受体(CCR6)在ATL中表达。脂肪细胞CCL20的表达与BMI呈正相关,且在内脏脂肪细胞中相比于皮下脂肪细胞有所增加。ATL表达炎症标志物并释放干扰素γ(IFNγ)。用ATL条件培养基处理祖细胞和脂肪细胞可降低胰岛素介导的生脂酶上调,这一效应涉及IFNγ。

结论

因此,人AT内的脂肪细胞和淋巴细胞之间存在相互作用,包括脂肪细胞对T细胞的趋化作用以及ATL对脂肪生成的调节作用。

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