Antigen- and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice.
Antigen- and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice.
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DOI：
10.1016/j.cmet.2015.03.005
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发表时间：
2015-04-07
期刊：
影响因子：
29
通讯作者：
Mathis D
中科院分区：
文献类型：
--
作者：
Kolodin D;van Panhuys N;Li C;Magnuson AM;Cipolletta D;Miller CM;Wagers A;Germain RN;Benoist C;Mathis D
一个独特的Foxp3+CD4+调节性T （Treg）细胞群，具有独特的转录组和抗原受体库，存在于瘦人的内脏脂肪组织（VAT）中。这些细胞调节局部炎症以及局部和全身代谢指标。在这里，我们将重点关注衰老瘦小鼠中VAT Treg区室的扩增——评估这些细胞从传统CD4+ T细胞的表型转化、淋巴器官的内流和局部种群动态。我们的研究结果证实，VAT Treg区室是由出生后最初几周产生的胸腺细胞播种的，并且由于惰性增殖（特别是某些克隆）而在10周龄后扩大，同时增加了存活率。VAT Tregs的积累依赖于MHC ii类分子呈递的抗原和可溶性介质，特别是白细胞介素(IL)-33。从治疗上解决这些因素有望利用Tregs来遏制日益流行的肥胖和随之而来的代谢异常的新方法。
A unique population of Foxp3+CD4+ regulatory T (Treg) cells, with a distinct transcriptome and antigen-receptor repertoire, resides in visceral adipose tissue (VAT) of lean individuals. These cells regulate local inflammation and both local and systemic metabolic indices. Here we focus on expansion of the VAT Treg compartment in aging lean mice – assessing these cells’ phenotypic conversion from conventional CD4+ T cells, influx from lymphoid organs, and local population dynamics. Our findings establish that the VAT Treg compartment is seeded from thymocytes generated during the first weeks of life, and expands beyond 10 weeks of age due to indolent proliferation, of certain clones in particular, coupled with enhanced survival. Accumulation of VAT Tregs depends on antigen(s) presented by MHC class-II molecules and soluble mediators, notably interleukin(IL)-33. Addressing such factors therapeutically promises novel approaches for harnessing Tregs to stem the growing epidemic of obesity and consequent metabolic abnormalities.