Anna Carey, Louise E Pitcher, In Hwa Jang, Katie Nguyen, Stephanie Cholensky, Paul D Robbins, Christina D Camell
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引用次数: 0
摘要
髓系细胞产生的白细胞介素-1β(IL-1β)推动了内脏脂肪组织(vWAT)的炎症反应,并促进了白细胞介素-1受体1(Il1r1)阳性老年脂肪B细胞(AABs)的扩张。在炎症挑战下,AABs 会促进代谢功能障碍和炎症。然而,目前还不清楚IL-1β是否在衰老过程中导致了与AAB相关的炎症。我们利用特异性 B 细胞 Il1r1 基因敲除(BKO 小鼠),研究了在没有 IL-1β - B 细胞信号传导的情况下老年 vWAT 的特征。除了雌性小鼠的性别特异性代谢改善外,我们还发现在 BKO vWAT 中,B 细胞的比例减少,B1:B2 B 细胞比率的性别特异性增加。通过vWAT免疫细胞的单细胞RNA测序,我们观察到BKO对vWAT免疫细胞的炎症信号传导产生了不同程度的影响。这些数据表明,IL-1β - B 细胞信号支持多种细胞类型的炎症反应,并为了解老龄 vWAT 复杂的微环境提供了线索。
B-cell Interleukin 1 Receptor 1 (IL1R1) modulates the female adipose tissue immune microenvironment during aging.
Myeloid cell production of interleukin-1β (IL-1β) drives inflammaging in visceral 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, it is unclear whether IL-1β contributes to AAB-associated inflammation during aging. 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.
期刊介绍:
JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.