M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue
M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue
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DOI：
10.1038/cmi.2017.11
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发表时间：
2018-05
影响因子：
24.1
通讯作者：
Huimin Zhang;Rufeng Xue;Shasha Zhu;Sicheng Fu;Zuolong Chen;Rongbin Zhou;Z. Tian;L. Bai
中科院分区：
文献类型：
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作者：
Huimin Zhang;Rufeng Xue;Shasha Zhu;Sicheng Fu;Zuolong Chen;Rongbin Zhou;Z. Tian;L. Bai
代谢反应与多种代谢综合征有关，如2型糖尿病。然而，代谢紊乱引发代谢转化的机制仍不清楚。我们发现，在内脏脂肪组织炎症发生之前，肥胖进展过程中M2巨噬细胞中CD1d表达的细胞类型特异性下调。CD1d表达的降低影响了M2巨噬细胞提呈抗原的能力，并导致抗原提呈细胞由M2巨噬细胞变为M1巨噬细胞。在CD1d条件性基因敲除(KO)小鼠中，我们进一步证明了M2巨噬细胞激活自然杀伤T(NKT)细胞通过促进肥胖小鼠内脏脂肪组织中Th2应答和M2极化来抑制代谢和胰岛素抵抗，而M1巨噬细胞激活NKT细胞通过促进Th1应答和抑制M2极化来加剧代谢和胰岛素抵抗。我们的结果表明，M2特异性的CD1d减少是一个启动事件，它切换了NKT细胞介导的免疫反应，破坏了肥胖小鼠内脏脂肪组织的免疫平衡。
Metaflammation is responsible for several metabolic syndromes, such as type 2 diabetes. However, the mechanisms by which metabolic disorders trigger metaflammation remain unclear. We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues. A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages. With CD1d conditional knockout (KO) mice, we further demonstrated that natural killer T (NKT) cell activation by M2 macrophages inhibited metaflammation and insulin resistance by promoting Th2 responses and M2 polarization in visceral adipose tissues of obese mice, whereas NKT cell activation by M1 macrophages exacerbated metaflammation and insulin resistance by promoting Th1 responses and inhibiting M2 polarization. Our results suggest that an M2-specific reduction of CD1d is an initiating event that switches NKT cell-mediated immune responses and disrupts the immune balance in visceral adipose tissues in obese mice.