Fatty acid-binding protein 5 limits ILC2-mediated allergic lung inflammation in a murine asthma model.
Fatty acid-binding protein 5 limits ILC2-mediated allergic lung inflammation in a murine asthma model.
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DOI：
10.1038/s41598-020-73935-y
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发表时间：
2020-10-06
影响因子：
4.6
通讯作者：
Owada Y
中科院分区：
文献类型：
--
作者：
Kobayashi S;Tayama S;Phung HT;Kagawa Y;Miyazaki H;Takahashi Y;Maruyama T;Ishii N;Owada Y
饮食性肥胖是一个世界性的问题，肥胖与过敏性炎症之间有着密切的联系。脂肪酸结合蛋白5 （Fatty acid binding protein 5, FABP5）在肺泡上皮细胞（alveolar epithelial cells, ECs）和肺泡巨噬细胞等肺细胞中表达，在肺部感染性炎症中起重要作用。然而，我们不知道肺脂质代谢变化如何影响过敏性肺部炎症的确切机制。在这项研究中，我们发现Fabp5−/−小鼠表现出严重的过敏性肺部炎症症状。我们试图研究FABP5在变应性肺炎症中的作用，并证明FABP5的表达在肺泡ECs中作为ST2表达的一种新的正调节因子，以产生视黄酸（RA），并支持II型肺泡ECs合成RA，以抑制过敏性肺炎症期间先天淋巴样细胞（ILC） 2的过度激活。此外，与正常饮食（ND）喂养的小鼠相比，高脂饮食（HFD）喂养的小鼠肺组织FABP5和ST2表达下调。这些现象可能是肥胖者更容易患过敏性肺部炎症的原因。因此，FABP5可能是治疗ilc2介导的过敏性肺部炎症的潜在治疗靶点。
Dietary obesity is regarded as a problem worldwide, and it has been revealed the strong linkage between obesity and allergic inflammation. Fatty acid-binding protein 5 (FABP5) is expressed in lung cells, such as alveolar epithelial cells (ECs) and alveolar macrophages, and plays an important role in infectious lung inflammation. However, we do not know precise mechanisms on how lipid metabolic change in the lung affects allergic lung inflammation. In this study, we showed that Fabp5−/− mice exhibited a severe symptom of allergic lung inflammation. We sought to examine the role of FABP5 in the allergic lung inflammation and demonstrated that the expression of FABP5 acts as a novel positive regulator of ST2 expression in alveolar ECs to generate retinoic acid (RA) and supports the synthesis of RA from type II alveolar ECs to suppress excessive activation of innate lymphoid cell (ILC) 2 during allergic lung inflammation. Furthermore, high-fat diet (HFD)-fed mice exhibit the downregulation of FABP5 and ST2 expression in the lung tissue compared with normal diet (ND)-fed mice. These phenomena might be the reason why obese people are more susceptible to allergic lung inflammation. Thus, FABP5 is potentially a therapeutic target for treating ILC2-mediated allergic lung inflammation.
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影响因子：
32.4
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
通讯作者：
Takei, Fumio
影响因子：
24.3
作者：
Hind, M;Maden, M
通讯作者：
Maden, M
影响因子：
7.7
作者：
Maeda, K;Uysal, KT;Hotamisligil, GS
通讯作者：
Hotamisligil, GS
影响因子：
14.2
作者：
Beasley, R;Crane, J;Pearce, N
通讯作者：
Pearce, N
DOI：
10.4049/jimmunol.0804192
发表时间：
2009-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Li B;Reynolds JM;Stout RD;Bernlohr DA;Suttles J
通讯作者：
Suttles J