Department of Immunology, Harvard Medical School and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Immunology & Inflammation Therapeutic Area, Sanofi US, Cambridge, MA 02139, USA.
Sci Immunol. 2019 May 3;4(35). doi: 10.1126/sciimmunol.aaw3658.
Regulatory T cells (T) are key brakes on the visceral adipose tissue (VAT) inflammation that regulates local and systemic metabolic tenor. Breakdown of this regulation promotes type 2 diabetes. The cytokine IL-33 expands and sustains the unique T population residing within VAT. Here, relying on single-cell RNA sequencing, we identified the major IL-33 producers in VAT to be particular mesenchymal stromal cell subtypes, related to but distinct from adipocyte progenitor cells. We explored modulation of the VAT stromal cell landscape with physiologic variables such as age and sex, as well as its remodeling in pathogenic states like obesity. Last, we uncovered a VAT T:stromal cell negative regulatory loop that keeps the potent effect of IL-33 under rein.
调节性 T 细胞(T 细胞)是调节内脏脂肪组织(VAT)炎症的关键制动器,这种炎症调节着局部和全身的代谢基调。这种调节的崩溃会促进 2 型糖尿病的发生。细胞因子 IL-33 会扩增并维持驻留在 VAT 中的独特 T 细胞群体。在这里,我们依赖单细胞 RNA 测序,确定 VAT 中主要的 IL-33 产生细胞为特定的间充质基质细胞亚型,与脂肪细胞祖细胞有关,但又与之不同。我们探讨了生理变量(如年龄和性别)对 VAT 基质细胞景观的调节,以及肥胖等病态下的重塑。最后,我们揭示了 VAT T 细胞:基质细胞负反馈调节环路,使 IL-33 的强大作用受到抑制。