Type 2 cytokines are important signals triggering biogenesis of thermogenic beige adipocytes in white adipose tissue (WAT) during cold acclimation. However, how cold activates type 2 immunity in WAT remains obscure. Here we show that cold-induced type 2 immune responses and beiging in subcutaneous WAT (scWAT) are abrogated in mice with adipose-selective ablation of FGF21 or its co-receptor β-Klotho, whereas such impairments are reversed by replenishment with chemokine CCL11. Mechanistically, FGF21 acts on adipocytes in an autocrine manner to promote the expression and secretion of CCL11 via activation of ERK1/2, which drives recruitment of eosinophils into scWAT, leading to increases in accumulation of M2 macrophages, and proliferation and commitment of adipocyte precursors into beige adipocytes. These FGF21-elicited type 2 immune responses and beiging are blocked by CCL11 neutralization. Thus, the adipose-derived FGF21-CCL11 axis triggers cold-induced beiging and thermogenesis by coupling sympathetic nervous system to activation of type 2 immunity in scWAT.

中文翻译：

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FGF21-CCL11轴通过将交感神经系统耦合到2型免疫来介导白色脂肪组织的变黄。

2型细胞因子是触发冷驯化过程中触发白色脂肪组织（WAT）中产热米色脂肪细胞生物发生的重要信号。但是，冷如何激活WAT中的2型免疫力仍然不清楚。在这里，我们显示在FGF21或其共受体β-Klotho的脂肪选择性消融小鼠中，冷诱导的2型免疫反应和皮下WAT（scWAT）中的白化现象被消除，而通过补充趋化因子CCL11可以逆转这种损伤。从机制上讲，FGF21通过激活ERK1 / 2以自分泌方式作用于脂肪细胞，从而促进CCL11的表达和分泌，从而促使嗜酸性粒细胞募集到scWAT中，导致M2巨噬细胞的积累增加，以及脂肪细胞前体的增殖和定型。米色脂肪细胞。这些由FGF21引起的2型免疫反应和白蛋白被CCL11中和作用所阻断。因此，脂肪来源的FGF21-CCL11轴通过将交感神经系统与scWAT中2型免疫的激活相结合，触发了冷诱导的成虫和生热作用。