Adipose tissue macrophages induce PPARγ-high FOXP3(+) regulatory T cells.
Adipose tissue macrophages induce PPARγ-high FOXP3(+) regulatory T cells.
复制标题
DOI：
10.1038/srep16801
复制
发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
Shimomura I
中科院分区：
文献类型：
--
作者：
Onodera T;Fukuhara A;Jang MH;Shin J;Aoi K;Kikuta J;Otsuki M;Ishii M;Shimomura I
与其他淋巴或非淋巴组织相比，脂肪组织中存在大量调节性T细胞（Tcells）。脂肪紧张素调节炎症状态和胰岛素敏感性。然而，在脂肪组织中维持TdR的机制仍不清楚。在这里，我们揭示了脂肪组织巨噬细胞（ATM）的诱导和增殖的脂肪T细胞的贡献。与脾树突状细胞相比，在稳态条件下从小鼠分离的ATM在体外诱导了具有高表达PPARγ的TcR。此外，来自肥胖小鼠的ATM促进了PPARγ低T细胞的分化。在体内，ATMs的连续转移可诱导Tcells的分化和增殖，而氯膦酸盐-脂质体消耗ATMs导致脂肪Tcells减少。抗炎脂肪细胞因子Adipoq的缺乏导致小比例的ATM和脂肪THBG，而不改变体内的其他免疫细胞。因此，这些数据表明，脂肪组织中丰富的Tcl 3可能部分归因于ATM诱导表达PPARγ的Tcl 3的能力。
Numerous regulatory T cells (Tregs) are present in adipose tissues compared with other lymphoid or non-lymphoid tissues. Adipose Tregs regulate inflammatory state and insulin sensitivity. However, the mechanism that maintains Tregs in adipose tissue remains unclear. Here, we revealed the contribution of adipose tissue macrophages (ATMs) to the induction and proliferation of adipose Tregs. ATMs isolated from mice under steady state conditions induced Tregs with high expression of PPARγ compared with splenic dendritic cells in vitro. Furthermore, ATMs from obese mice prompted the differentiation of PPARγ low Tregs. Adoptive transfer of ATMs induced differentiation and proliferation of Tregs, whereas depletion of ATMs by clodronate-liposome resulted in reduction of adipose Tregs, in vivo. Deficiency of anti-inflammatory adipocytokine, Adipoq, resulted in small proportions of ATMs and adipose Tregs without alteration of other immune cells in vivo. Therefore, these data suggest that the abundance of Tregs in adipose tissue could be partly attributed to the ability of ATMs to induce PPARγ-expressing Tregs.