4.6 Article

Myeloid Cell-Specific IL-4 Receptor Knockout Partially Protects from Adipose Tissue Inflammation

期刊

JOURNAL OF IMMUNOLOGY
卷 207, 期 12, 页码 3081-3089

出版社

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2100699

关键词

-

资金

  1. Deutsche Forschungsgemeinschaft (German Research Foundation) [(SFB) 1052, 209933838]
  2. Federal Ministry of Education and Research, Germany, Integrated Research and Treatment Center (IFB) Adiposity Diseases [01EO1501]
  3. Deutsche Forschungsgemeinschaft [SFB1052/2]
  4. Federal Ministry of Education and Research, Germany, IFB Adiposity Diseases [01EO1501]
  5. German Research Center for Diabetes [82DZD00601]
  6. German Diabetes Association [934300-003]

向作者/读者索取更多资源

This study suggests that IL-4 receptor signaling plays a minor role in maintaining the macrophage M2 population and proliferation rates in vivo, while IL-4 signaling exerts a proinflammatory role in adipose tissue inflammation by directly upregulating CD11c on adipose tissue macrophages.
IL-4 receptor signaling is supposed to play a major role in anti-inflammatory polarization and proliferation of adipose tissue macrophages. In this study, we examined the metabolic and inflammatory phenotype of C57BL/6J mice (IIl4ra) with LysM-dependent knockout (IIl4ra(Delta myel)) of the IL-4 receptor alpha-chain (IL-4R alpha), the mandatory signaling component of IL-4 and IL-13, on chow and high-fat diet. Lean IIl4ra(Delta myel) mice showed decreased insulin sensitivity, no divergent adipose tissue macrophage polarization, but an increased percentage of CD8(+) T cells in visceral adipose tissue. After 20 wk of a high-fat diet, IIl4ra(Delta myel) mice exhibited higher glucose tolerance, no changes in the lymphocyte compartment and fewer M1 macrophages in visceral adipose tissue. In vivo adipose tissue macrophage proliferation measured by BrdU incorporation was unaffected by Il4ra knockout. Interestingly, we show that IL-4R alpha signaling directly augmented Itgax (Cd11c) gene expression in bone marrow-derived macrophages and increased the amount of CD11c(+) macrophages in adipose tissue explants. Myeloid cell -specific knockout of Il4ra deteriorated insulin sensitivity in lean mice but improved parameters of glucose homeostasis and partially protected from adipose tissue inflammation in obese mice. Hence, IL-4R alpha signaling probably plays a minor role in maintaining the macrophage M2 population and proliferation rates in vivo. Moreover, our data indicate that IL-4 signaling plays a proinflammatory role in adipose tissue inflammation by directly upregulating CD11c on adipose tissue macrophages.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据