Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3⁺ regulatory T cells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how T cells interlink environmental influences with adipocyte function remains unknown. Here, we report that enhancing sympathetic tone by cold exposure, beta3-adrenergic receptor (ADRB3) stimulation or a short-term high-calorie diet enhances Treg induction in vitro and in vivo. CD4⁺ T cell proteomes revealed higher expression of Foxp3 regulatory networks in response to cold or ADRB3 stimulation in vivo reflecting Treg induction. Specifically, Ragulator-interacting protein C17orf59, which limits mTORC1 activity, was upregulated in CD4⁺ T cells by either ADRB3 stimulation or cold exposure, suggesting contribution to Treg induction. By loss- and gain-of-function studies, including Treg depletion and transfers in vivo, we demonstrated that a T cell-specific Stat6/Pten axis links cold exposure or ADRB3 stimulation with Foxp3⁺ Treg induction and adipose tissue function. Our findings offer a new mechanistic model in which tissue-specific Tregs maintain adipose tissue function.

中文翻译：

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Stat6 / Pten轴连接具有脂肪组织功能的调节性T细胞。

肥胖和2型糖尿病与代谢缺陷和脂肪组织炎症有关。Foxp3 ⁺调节性T细胞（Tregs）通过抵消局部炎症来控制组织稳态。然而，尚不清楚T细胞是否以及如何将环境影响与脂肪细胞功能联系起来。在这里，我们报道通过冷暴露，β3-肾上腺素能受体（ADRB3）刺激或短期高热量饮食来增强交感神经张力，可在体外和体内增强Treg的诱导作用。CD4 ⁺ T细胞蛋白质组揭示了在体内对Treg诱导的冷刺激或ADRB3刺激后，Foxp3调控网络的表达更高。具体而言，限制mTORC1活性的与Ragulator相互作用的蛋白C17orf59在CD4 ^+中上调通过ADRB3刺激或冷暴露引起的T细胞，提示其对Treg的诱导作用。通过功能丧失和获得功能的研究，包括体内Treg的耗竭和转移，我们证明了T细胞特异性Stat6 / Pten轴将冷暴露或ADRB3刺激与Foxp3 ⁺ Treg诱导和脂肪组织功能联系起来。我们的发现提供了一种新的机制模型，其中组织特异性Treg维持脂肪组织功能。