Regulatory T (Treg) cells in epidydimal visceral adipose tissue (eVAT) of lean mice and humans regulate metabolic homeostasis. We found that constitutive or punctual depletion of eVAT-Treg cells reined in the differentiation of stromal adipocyte precursors. Co-culture of these precursors with conditional medium from eVAT-Treg cells limited their differentiation in vitro, suggesting a direct effect. Transcriptional comparison of adipocyte precursors, matured in the presence or absence of the eVAT-Treg-conditioned medium, identified the oncostatin-M (OSM) signaling pathway as a key distinction. Addition of OSM to in vitro cultures blocked the differentiation of adipocyte precursors, while co-addition of anti-OSM antibodies reversed the ability of the eVAT-Treg-conditioned medium to inhibit in vitro adipogenesis. Genetic depletion of OSM (specifically in Treg) cells or of the OSM receptor (specifically on stromal cells) strongly impaired insulin sensitivity and related metabolic indices. Thus, Treg-cell-mediated control of local progenitor cells maintains adipose tissue and metabolic homeostasis, a regulatory axis seemingly conserved in humans.

瘦小鼠和人类附睾内脏脂肪组织 (eVAT) 中的调节性 T (Treg) 细胞调节代谢稳态。我们发现 eVAT-Treg 细胞的组成性或点时耗竭抑制了基质脂肪细胞前体的分化。这些前体细胞与来自 eVAT-Treg 细胞的条件培养基的共培养限制了它们的体外分化，表明有直接作用。对在存在或不存在 eVAT-Treg 条件培养基的情况下成熟的脂肪细胞前体进行转录比较，确定制瘤素-M (OSM) 信号通路是一个关键区别。在体外培养物中添加 OSM会阻断脂肪细胞前体的分化，而同时添加抗 OSM 抗体则逆转了 eVAT-Treg 条件培养基抑制体外脂肪生成的能力。 OSM（特别是 Treg）细胞或 OSM 受体（特别是基质细胞）的基因耗竭会严重损害胰岛素敏感性和相关代谢指标。因此，Treg 细胞介导的对局部祖细胞的控制维持了脂肪组织和代谢稳态，这一调节轴似乎在人类中保守。