Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.
Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.
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DOI：
10.1016/j.immuni.2012.06.016
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发表时间：
2012-09-21
期刊：
影响因子：
32.4
通讯作者：
Exley MA
中科院分区：
文献类型：
--
作者：
Lynch L;Nowak M;Varghese B;Clark J;Hogan AE;Toxavidis V;Balk SP;O'Shea D;O'Farrelly C;Exley MA
不变性自然杀伤T细胞（iNKT）是进化上保守的先天T细胞，影响炎症反应。我们已经证明iNKT细胞，以前被认为在人类中很少见，在人类和小鼠脂肪组织中高度富集，并且随着肥胖脂肪组织的扩张，iNKT细胞被耗尽，与促炎巨噬细胞浸润相关。体重减轻后，小鼠和人类的iNKT细胞数量恢复。缺乏iNKT细胞的小鼠在高脂肪饮食中体重增加、脂肪细胞增大、脂肪肝和胰岛素抵抗。将iNKT细胞过继转移到肥胖小鼠体内，或利用其脂质配体α -半乳糖神经酰胺在体内激活iNKT细胞，可降低体脂、甘油三酯、瘦素、脂肪肝，并通过脂肪来源的iNKT细胞产生Th2细胞型细胞因子改善胰岛素敏感性。这一发现突出了iNKT细胞靶向治疗在肥胖及其后果管理方面的潜力，此前已被证明对人类是安全的。
Invariant Natural Killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in huamns, were highly enriched in human and murine adipose tissue, and that as adipose tissue expands in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers and insulin resistance on high fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells with their lipid ligand alpha-galactocylceramide decreased body fat, triglycerides, leptin, fatty liver, and improved insulin sensitivity through Th2 cell-type cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.