Carey Anna, Pitcher Louise E, Jang In Hwa, Nguyen Katie, Cholensky Stephanie, Robbins Paul D, Camell Christina D
Molecular Pharmacology and Therapeutics Graduate Program, Department of Pharmacology, University of Minnesota, 312 Church Street SE, Minneapolis, MN 55455, United States.
Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, 312 Church Street SE, Minneapolis, MN 55455, United States.
J Leukoc Biol. 2025 Feb 13;117(2). doi: 10.1093/jleuko/qiae219.
Myeloid cell production of interleukin-1β (IL-1β) drives inflammaging in visceral white adipose tissue (vWAT) and contributes to the expansion of interleukin-1 receptor 1 (Il1r1)-positive aged adipose B cells (AABs). AABs promote metabolic dysfunction and inflammation under inflammatory challenges. However, whether IL-1β contributes to AAB-associated inflammation during aging is unclear. Using a B-cell-specific knockout of Il1r1 (BKO mice), we characterized old vWAT in the absence of IL-1β-B-cell signaling. In addition to sex-specific metabolic improvements in females, we identified a reduction in the proportion of B cells and a sex-specific increase in the B1/B2 B-cell ratio in BKO vWAT. Using single-cell RNA sequencing of vWAT immune cells, we observed that BKO differentially affected inflammatory signaling in vWAT immune cells. These data suggest that IL-1β-B-cell signaling supports the inflammatory response in multiple cell types and provides insight into the complex microenvironment in aged vWAT.
髓样细胞产生的白细胞介素-1β（IL-1β）驱动内脏白色脂肪组织（vWAT）中的炎症衰老，并促进白细胞介素-1受体1（Il1r1）阳性的衰老脂肪B细胞（AABs）的扩增。在炎症刺激下，AABs会促进代谢功能障碍和炎症反应。然而，IL-1β在衰老过程中是否会导致与AAB相关的炎症尚不清楚。我们利用B细胞特异性敲除Il1r1（BKO小鼠），对缺乏IL-1β-B细胞信号传导的老年vWAT进行了表征。除了雌性小鼠有性别特异性的代谢改善外，我们还发现BKO vWAT中B细胞比例降低，且B1/B2 B细胞比率有性别特异性增加。通过对vWAT免疫细胞进行单细胞RNA测序，我们观察到BKO对vWAT免疫细胞中的炎症信号传导有不同影响。这些数据表明，IL-1β-B细胞信号传导支持多种细胞类型中的炎症反应，并为老年vWAT中复杂的微环境提供了见解。
