Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Immunol. 2013 Jun;43(6):1578-87. doi: 10.1002/eji.201243096. Epub 2013 Apr 24.
Adipose tissue contains several immune cells whose number and phenotype vary depending on the adiposity. In the present study, we show that IFN-γ(+) CD4(+) T cells are enriched in human adipose tissue compared with in blood. To gain insight into the underlying mechanisms, we investigated the possibility that human adipocytes modulate CD4(+) T-cell cytokine production and proliferation and show that CD4(+) T cells produced increased levels of IFN-γ when activated in the presence of adipocytes. This effect was mediated by soluble mediators, as shown in transwell and adipocyte-conditioned medium (ACM) transfer experiments. Additionally, ACM induced increased proliferation of CD4(+) T cells upon activation. Intriguingly, the proliferation-enhancing effect resided mainly in the lipid fraction of ACM, as shown upon separation of the protein and lipid fraction. Further separation of these lipids based on polarity revealed that the modulatory effect is confined to fractions containing free fatty acids. All identified fatty acids were able to individually enhance T-cell proliferation. These data indicate that adipocytes can modulate CD4(+) T-cell function through the release of lipids. Remarkably, free fatty acids were the most prominent modulators of T-cell proliferation, possibly leading to an accumulation of these cells in adipose tissue.
脂肪组织中含有多种免疫细胞，其数量和表型根据肥胖程度而变化。在本研究中，我们发现与血液相比，IFN-γ(+) CD4(+) T 细胞在人类脂肪组织中更为丰富。为了深入了解潜在的机制，我们研究了脂肪细胞是否能够调节 CD4(+) T 细胞细胞因子的产生和增殖的可能性，并表明在脂肪细胞存在的情况下，CD4(+) T 细胞的激活会增加 IFN-γ的产生。这种效应是由可溶性介质介导的，如 Transwell 和脂肪细胞条件培养基 (ACM) 转移实验所示。此外，ACM 在激活时诱导 CD4(+) T 细胞的增殖增加。有趣的是，增殖增强效应主要存在于 ACM 的脂质部分，如在分离蛋白质和脂质部分后所示。进一步根据极性对这些脂质进行分离表明，调节作用仅限于含有游离脂肪酸的部分。所有鉴定出的脂肪酸都能够单独增强 T 细胞的增殖。这些数据表明，脂肪细胞可以通过释放脂质来调节 CD4(+) T 细胞的功能。值得注意的是，游离脂肪酸是 T 细胞增殖的最主要调节剂，可能导致这些细胞在脂肪组织中的积累。
