Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis
Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis
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DOI：
10.1016/j.cmet.2019.10.006
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发表时间：
2019-12-03
期刊：
影响因子：
29
通讯作者：
Dixit, Vishwa Deep
中科院分区：
文献类型：
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作者：
Camell, Christina D.;Guenther, Patrick;Dixit, Vishwa Deep
在衰老过程中，内脏肥胖通常与脂肪组织（AT）白细胞、炎症和代谢功能障碍的改变有关。然而，AT B细胞在衰老过程中的免疫代谢中的作用尚未研究。在这里，我们表明，衰老与一个独特的人口的居民非衰老的老年脂肪B细胞（AAB）的脂肪相关淋巴簇（AQC）中发现的扩展。AAB在转录上不同于脾年龄相关B细胞（ABC），并在雌性小鼠中显示出更大的扩增。在功能上，全身B细胞消耗恢复适当的脂解和核心体温维持在寒冷的压力。从机制上讲，年龄诱导的CD 4C形成、AAB和脾ABC扩张依赖于Nlrp 3炎性小体。此外，AAB表达IL-1 R，并且IL-1信号传导的抑制降低它们的增殖并增加衰老中的脂解。这些数据表明，抑制Nlrp 3依赖性B细胞积累可以靶向逆转衰老AT中的代谢损伤。
During aging, visceral adiposity is often associated with alterations in adipose tissue (AT) leukocytes, inflammation, and metabolic dysfunction. However, the contribution of AT B cells in immunometabolism during aging is unexplored. Here, we show that aging is associated with an expansion of a unique population of resident non-senescent aged adipose B cells (AABs) found in fat-associated lymphoid clusters (FALCs). AABs are transcriptionally distinct from splenic age-associated B cells (ABCs) and show greater expansion in female mice. Functionally, whole-body B cell depletion restores proper lipolysis and core body temperature maintenance during cold stress. Mechanistically, the age-induced FALC formation, AAB, and splenic ABC expansion is dependent on the Nlrp3 inflammasome. Furthermore, AABs express IL-1R, and inhibition of IL-1 signaling reduces their proliferation and increases lipolysis in aging. These data reveal that inhibiting Nlrp3-dependent B cell accumulation can be targeted to reverse metabolic impairment in aging AT.