The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor α1 (IL13Rα1)
The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor α1 (IL13Rα1)
复制标题
DOI：
10.1074/jbc.m110.169367
复制
发表时间：
2011-01-21
影响因子：
4.8
通讯作者：
Sanchez-Elsner, Tilman
中科院分区：
文献类型：
--
作者：
Martinez-Nunez, Rocio T.;Louafi, Fethi;Sanchez-Elsner, Tilman
巨噬细胞在免疫反应的平衡和效率中起着核心作用，是先天免疫和适应性免疫之间的接口。他们的表型是M1（经典的，亲th -1）和M2（替代的，亲th -2）之间的微妙平衡。这种平衡由白细胞介素13 （IL-13）等细胞因子调节，IL-13是一种典型的促m2 - th -2细胞因子，与过敏性疾病和哮喘有关。IL-13与II型IL-4受体的组分IL-13受体α 1 （IL13R α 1）结合，通过磷酸化激活转录因子信号换能器和转录激活因子6 （STAT6）发挥作用。microrna是短的（类似于22个核苷酸）抑制非编码rna，阻断其特定mRNA靶标的翻译或促进其降解。通过生物信息学分析，我们发现microRNA-155 （miR-155）被预测靶向IL13R α 1。这表明miR-155可能通过调节IL-13的作用参与巨噬细胞中M1/M2平衡的调节。miR-155与健康免疫系统和功能的发展以及炎症前th -1/M1免疫谱有关。在这里，我们已经证明，在人巨噬细胞中，miR-155直接靶向IL13R α 1并降低IL13R α 1蛋白的水平，导致STAT6的激活减弱。最后，我们还证明miR-155影响il -13依赖性的几个基因（SOCS1、DC-SIGN、CCL18、CD23和SERPINE）的调节，这些基因参与巨噬细胞中M2/pro-Th-2表型的建立。我们的工作表明miR-155在确定人巨噬细胞M2表型中的核心作用。
Macrophages play a central role in the balance and efficiency of the immune response and are at the interface between innate and adaptive immunity. Their phenotype is a delicate equilibrium between the M1 (classical, pro-Th-1) and M2 (alternative, pro-Th-2) profiles. This balance is regulated by cytokines such as interleukin 13 (IL-13), a typical pro-M2-Th-2 cytokine that has been related to allergic disease and asthma. IL-13 binds to IL-13 receptor alpha 1 (IL13R alpha 1), a component of the Type II IL-4 receptor, and exerts its effects by activating the transcription factor signal transducer and activator of transcription 6 (STAT6) through phosphorylation. MicroRNAs are short (similar to 22 nucleotide) inhibitory non-coding RNAs that block the translation or promote the degradation of their specific mRNA targets. By bioinformatics analysis, we found that microRNA-155 (miR-155) is predicted to target IL13R alpha 1. This suggested that miR-155 might be involved in the regulation of the M1/M2 balance in macrophages by modulating IL-13 effects. miR-155 has been implicated in the development of a healthy immune system and function as well as in the inflammatory pro-Th-1/M1 immune profile. Here we have shown that in human macrophages, miR-155 directly targets IL13R alpha 1 and reduces the levels of IL13R alpha 1 protein, leading to diminished activation of STAT6. Finally we also demonstrate that miR-155 affects the IL-13-dependent regulation of several genes (SOCS1, DC-SIGN, CCL18, CD23, and SERPINE) involved in the establishment of an M2/pro-Th-2 phenotype in macrophages. Our work shows a central role for miR-155 in determining the M2 phenotype in human macrophages.