Kolodin Dmitriy, van Panhuys Nicolas, Li Chaoran, Magnuson Angela M, Cipolletta Daniela, Miller Christine M, Wagers Amy, Germain Ronald N, Benoist Christophe, Mathis Diane
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Cell Metab. 2015 Apr 7;21(4):543-57. doi: 10.1016/j.cmet.2015.03.005.
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 the 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.
在瘦人的内脏脂肪组织（VAT）中，存在着一群独特的Foxp3(+)CD4(+)调节性T（Treg）细胞，它们具有独特的转录组和抗原受体库。这些细胞调节局部炎症以及局部和全身代谢指标。在这里，我们聚焦于衰老瘦小鼠中VAT Treg区室的扩张，评估这些细胞从传统CD4(+) T细胞的表型转化、来自淋巴器官的流入以及局部群体动态。我们的研究结果表明，VAT Treg区室由生命最初几周产生的胸腺细胞播种，并在10周龄后由于特别是某些克隆的惰性增殖以及存活率提高而扩大。VAT Tregs的积累取决于MHC II类分子呈递的抗原和可溶性介质，尤其是白细胞介素（IL）-33。通过治疗解决这些因素有望为利用Tregs来阻止肥胖及随之而来的代谢异常的日益流行提供新方法。
