Regulatory T cells (Treg cells) are important for preventing autoimmunity and maintaining tissue homeostasis, but whether Treg cells can adopt tissue- or immune-context-specific suppressive mechanisms is unclear. Here, we found that the enzyme hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes prostaglandin E₂ (PGE₂) into the metabolite 15-keto PGE₂, was highly expressed in Treg cells, particularly those in visceral adipose tissue (VAT). Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ)-induced HPGD expression in VAT Treg cells, and consequential Treg-cell-mediated generation of 15-keto PGE₂ suppressed conventional T cell activation and proliferation. Conditional deletion of Hpgd in mouse Treg cells resulted in the accumulation of functionally impaired Treg cells specifically in VAT, causing local inflammation and systemic insulin resistance. Consistent with this mechanism, humans with type 2 diabetes showed decreased HPGD expression in Treg cells. These data indicate that HPGD-mediated suppression is a tissue- and context-dependent suppressive mechanism used by Treg cells to maintain adipose tissue homeostasis.

调节性T细胞（Treg细胞）对于预防自身免疫和维持组织动态平衡很重要，但是尚不清楚Treg细胞是否可以采用组织特异性或免疫特异性的抑制机制。在这里，我们发现，将前列腺素E ₂（PGE ₂）分解为代谢物15-酮PGE ₂的酶羟前列腺素脱氢酶（HPGD）在Treg细胞，特别是在内脏脂肪组织（VAT）中高表达。核受体过氧化物酶体增殖物激活受体-γ（PPARγ）诱导的增值税Treg细胞中的HPGD表达，以及相应的Treg细胞介导的15-酮PGE _2的生成抑制了常规T细胞的活化和增殖。小鼠Treg细胞中Hpgd的有条件缺失导致功能受损的Treg细胞特别是在VAT中积累，从而引起局部炎症和全身性胰岛素抵抗。与这种机制一致，患有2型糖尿病的人在Treg细胞中显示HPGD表达降低。这些数据表明，HPGD介导的抑制是Treg细胞用于维持脂肪组织动态平衡的组织和背景相关的抑制机制。