IL-37 inhibits the maturation of dendritic cells through the IL-1R8-TLR4-NF-κB pathway
IL-37 inhibits the maturation of dendritic cells through the IL-1R8-TLR4-NF-κB pathway
复制标题
IL-37通过IL-1R8-TLR4-NF-kappa B途径抑制树突状细胞的成熟
DOI：
10.1016/j.bbalip.2019.05.009
复制
发表时间：
2019-10-01
影响因子：
4.8
通讯作者：
Ji, Qingwei
中科院分区：
文献类型：
--
作者：
Liu, Tianxiao;Liu, Jing;Ji, Qingwei
成熟树突状细胞（dc）在动脉粥样硬化中起致病作用。我们之前的研究表明，外源性白细胞介素(IL)-37抑制dc成熟，诱导t -调节性（Treg）细胞反应，并减轻ApoE（-/-）小鼠的动脉粥样硬化。本研究旨在探讨IL-37在动脉粥样硬化发展过程中影响dc成熟的分子机制。白细胞介素-1受体8 （IL-1R8）的表达在ApoE（-/-）小鼠和IL-37转基因（IL-37tg） ApoE（-/-）小鼠中进行了检测。IL-1R8是一种igg结构域受体，最近被发现对IL-37、toll样受体（TLR） 4和p65的细胞外功能起关键作用。IL-1R8主要在主动脉斑块浸润的dc中表达，在IL-37tg动脉粥样硬化小鼠中表达水平显著升高，TLR4和p65表达水平较低。此外，IL-37消除氧化低密度脂蛋白（oxLDL）诱导的dc成熟，并在体外引起IL-1R8的显著上调，TLR4和p65的下调，这与小鼠实验结果一致。然而，当IL-37用于il - 1r8缺陷和tlr4缺陷小鼠分离的dc时，IL-37对dc体外成熟的抑制作用被消除。因此，本研究提示IL-37通过IL-1R8-TLR4-NF-kappa B途径抑制dc的成熟，减轻ApoE（-/-）小鼠的动脉粥样硬化。
Mature dendritic cells (DCs) play a pathogenic role in atherosclerosis. Our previous study demonstrated that exogenous interleukin (IL)-37 suppresses the maturation of DCs, induces the T-regulatory (Treg) cell response, and attenuates atherosclerosis in ApoE(-/-) mice. The aim of the present study was to explore the molecular mechanism of IL-37 on the maturation of DCs throughout the development of atherosclerosis. The expression of interleukin-1 receptor 8 (IL-1R8), which is a single Ig-domain receptor that was recently found to be pivotal for the extracellular function of IL-37, Toll-like receptor (TLR) 4 and p65, was measured in ApoE(-/-) mice and IL-37 transgenic (IL-37tg) ApoE(-/-) mice. IL-1R8 was mainly expressed in aortic plaque-infiltrated DCs and at significantly higher levels in IL-37tg atherosclerotic mice, accompanied by lower levels of TLR4 and p65. Furthermore, IL-37 eliminated the maturation of DCs induced by oxidized low-density lipoprotein (oxLDL) and caused marked upregulation of IL-1R8 in vitro and downregulation of TLR4 and p65, which was consistent with the experiments in mice. However, the inhibitory effect of IL-37 on the maturation of DCs in vitro was abolished when IL-37 was used to treat DCs isolated from IL-1R8-deficient and TLR4-deficient mice. Therefore, this study indicated that IL-37 inhibited the maturation of DCs via the IL-1R8-TLR4-NF-kappa B pathway and attenuated atherosclerosis in ApoE(-/-) mice.