Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn's disease
Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn's disease
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DOI：
10.1136/gutjnl-2011-301424
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发表时间：
2013-06-01
期刊：
影响因子：
24.5
通讯作者：
Siegmund, Britta
中科院分区：
文献类型：
--
作者：
Kredel, Lea Isabell;Batra, Arvind;Siegmund, Britta
目的克罗恩病（CD）患者的爬行脂肪内有巨噬细胞浸润，局部脂肪因子水平升高。本研究旨在将这些观察结果联系起来，以确定巨噬细胞在人类CD病理中的作用。方法将人类外周血CD14细胞在体外极化为M1和M2巨噬细胞。评估瘦素和脂联素治疗后对脂肪因子受体、表型表面标志物、细胞因子和趋化因子的影响。免疫组织化学显示了CD患者肠系膜脂肪组织样本中的巨噬细胞亚型。结果两种脂肪因子均能改变M1和M2巨噬细胞的表型和功能，但M2巨噬细胞对脂肪因子的敏感性更高。M1通过增加细胞因子的产生来响应瘦素，但是在具有高表达白细胞介素（IL）-10、IL-6和肿瘤坏死因子a的M2巨噬细胞中观察到更强的作用。脂联素发挥类似的作用，并导致上调甘露糖受体表达的M2巨噬细胞。CD患者肠系膜脂肪组织内大量巨噬细胞主要由M2巨噬细胞浸润，导致IL-10富集环境。虽然瘦素增加了这两种亚型吸引CD3 T细胞的效力，脂联素只影响M2 macrophages. Conclusion CD患者的蠕动脂肪内的脂肪细胞依赖的微环境调节局部巨噬细胞室的M2亚型的偏好。这项人类细胞研究的结果表明，肠系膜脂肪在CD中具有保护作用，因为它是一种具有限制肠道炎症潜力的包膜屏障。
Objective The creeping fat in Crohn's disease (CD) is infiltrated by macrophages; local adipokine levels are increased. This study aimed to link these observations to define a role for macrophages in the pathology of human CD.Methods Human peripheral blood CD14 cells were polarised in vitro into M1 and M2 macrophages. The effects on adipokine receptors, phenotypic surface markers, cytokines and chemokines were assessed after treatment with leptin and adiponectin. Immunohistochemistry visualised macrophage subtypes in samples of mesenteric fat tissue from patients with CD. The chemotactic potential of secreted macrophage products was determined by T cell migration and chemokine production in vitro.Results Although both adipokines altered the phenotype and function of M1 and M2 macrophages, M2 macrophages were more susceptible. M1 responded to leptin by increased cytokine production, but the stronger effect was seen in M2 macrophages with high expression of interleukin (IL)-10, IL-6 and tumour necrosis factor a. Adiponectin exerted similar effects and led to upregulated mannose receptor expression by M2 macrophages. Large macrophage numbers within the mesenteric fat tissue of patients with CD comprise a unique infiltration predominantly of M2 macrophages, leading to an IL-10-rich environment. While leptin increased the potency of both subtypes to attract CD3 T cells, adiponectin only affected M2 macrophages.Conclusion The adipocyte-dependent microenvironment within the creeping fat of patients with CD modulates the local macrophage compartment to a preference for the M2 subtype. The findings in this study with human cells suggest a protective role for the mesenteric fat in CD in terms of an enveloping barrier with the potential to limit intestinal inflammation.