IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge.
IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge.
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DOI：
10.1016/j.celrep.2017.03.046
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发表时间：
2017-04-11
期刊：
影响因子：
8.8
通讯作者：
Dixit VD
中科院分区：
文献类型：
--
作者：
Spadaro O;Camell CD;Bosurgi L;Nguyen KY;Youm YH;Rothlin CV;Dixit VD
巨噬细胞与它们的吞噬活性一致，被认为主要通过它们产生特定细胞因子和代谢物的能力来调节宿主的免疫代谢反应。本研究表明，IL-4分化的m2样巨噬细胞分泌IGF1，这是一种以前被认为仅由肝脏产生的激素。在喂食高脂饮食的小鼠中，骨髓细胞中IGF1受体的消融减少了吞噬作用，增加了脂肪组织中的巨噬细胞，增加了脂肪，降低了能量消耗，并导致胰岛素抵抗。肥胖骨髓IGF1R敲除（MIKO）中脂肪巨噬细胞表型的研究显示，与m2样巨噬细胞激活相关的转录物减少。此外，感染巴西尼波圆线虫的MIKO小鼠表现出胰岛素敏感性正常的延迟消退。令人惊讶的是，在对照组和MIKO小鼠的脂肪组织巨噬细胞中，冷刺激并没有引发明显的m2样状态，也没有诱导酪氨酸羟化酶的表达。这些结果表明IGF1信号决定了巨噬细胞的激活表型。内分泌IGF1具有多种功能，并向巨噬细胞提供信号以维持组织发育和稳态。在这项研究中，Spadaro等人表明，m2样巨噬细胞本身是IGF1的重要来源，并且髓源性IGF1R信号调节免疫代谢。宿主对高脂肪饮食诱导的肥胖和蠕虫清除的适应需要骨髓IGF1R，而不是对冷应激的反应。
In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here we show that IL-4 differentiated M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptor from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure and led to insulin-resistance in mice fed high fat diet. The investigation of adipose macrophage phenotype in obese myeloid IGF1R knock out (MIKO) revealed a reduction in transcripts associated with M2-like macrophage activation. Furthermore, the MIKO mice infected with helminth Nippostrongylus brasiliensis displayed delayed resolution from infection with normal insulin-sensitivity. Surprisingly, cold –challenge did not trigger overt M2-like state and failed to induce tyrosine hydroxylase expression in adipose tissue macrophages of control or MIKO mice. These results show that IGF1 signaling shapes the macrophage activation phenotype. Endocrine IGF1 plays pleiotropic functions and provides signals to macrophages to sustain tissue development and homeostasis. In this work Spadaro et al. show that M2-like macrophages are an important source of IGF1 itself and that the myeloid-derived IGF1R signaling regulates immune-metabolism. Host adaptation to high-fat diet induced obesity and helminth clearance requires myeloid IGF1R but not the response to cold-stress.
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影响因子：
64.8
作者：
Nguyen, Khoa D.;Qiu, Yifu;Cui, Xiaojin;Goh, Y. P. Sharon;Mwangi, Julia;David, Tovo;Mukundan, Lata;Brombacher, Frank;Locksley, Richard M.;Chawla, Ajay
通讯作者：
Chawla, Ajay
DOI：
10.1038/nri2528
发表时间：
2009-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
影响因子：
10.5
作者：
Fernández, AM;Kim, JK;Le Roith, D
通讯作者：
Le Roith, D