Adipose tissue dysfunction is strongly linked to the development of chronic inflammation and cardiometabolic disorders in aging. While much attention has been given to the role of resident adipose tissue immune cells in the disruption of homeostasis in obesity, age-specific effects remain understudied. Here, we identified and characterized a population of γδ T cells, which show unique age-dependent accumulation in the visceral adipose tissue (VAT) of both mice and humans. Diet-induced obesity likewise increased γδ T cell numbers; however, the effect was greater in the aged where the increase was independent of fat mass. γδ T cells in VAT express a tissue-resident memory T cell phenotype (CD44^hiCD62L^lowCD69⁺) and are predominantly IL-17A-producing cells. Transcriptome analyses of immunomagnetically purified γδ T cells identified significant age-associated differences in expression of genes related to inflammation, immune cell composition, and adipocyte differentiation, suggesting age-dependent qualitative changes in addition to the quantitative increase. Genetic deficiency of γδ T cells in old age improved the metabolic phenotype, characterized by increased respiratory exchange ratio, and lowered levels of IL-6 both systemically and locally in VAT. Decreased IL-6 was predominantly due to reduced production by non-immune stromal cells, primarily preadipocytes, and adipose-derived stem cells. Collectively, these findings suggest that an age-dependent increase of tissue-resident γδ T cells in VAT contributes to local and systemic chronic inflammation and metabolic dysfunction in aging.

脂肪组织功能障碍与衰老过程中慢性炎症和心脏代谢疾病的发展密切相关。虽然人们对常驻脂肪组织免疫细胞在破坏肥胖体内平衡中的作用给予了很多关注，但对特定年龄的影响仍未得到充分研究。在这里，我们鉴定并表征了一群 γδ T 细胞，它们在小鼠和人类的内脏脂肪组织 (VAT) 中表现出独特的年龄依赖性积累。饮食诱导的肥胖同样增加了 γδ T 细胞数量；然而，在增加与脂肪量无关的老年人中效果更大。VAT 中的 γδ T 细胞表达组织驻留记忆 T 细胞表型（CD44 ^hi CD62L ^low CD69 ⁺) 并且主要是产生 IL-17A 的细胞。免疫磁性纯化的 γδ T 细胞的转录组分析确定了与炎症、免疫细胞组成和脂肪细胞分化相关的基因表达与年龄相关的显着差异，这表明除了数量增加外，还存在与年龄相关的质变。老年 γδ T 细胞的遗传缺陷改善了代谢表型，其特征是呼吸交换率增加，并在 VAT 中全身和局部降低 IL-6 水平。IL-6 减少主要是由于非免疫基质细胞（主要是前脂肪细胞和脂肪来源的干细胞）的产生减少。集体，