Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation
Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation
复制标题
巨噬细胞在炎症的不同阶段通过调节Maf（微小染色体维持蛋白相关因子）的表达来转换其表型
DOI：
10.4049/jimmunol.1800040
复制
发表时间：
2018-07-15
影响因子：
4.4
通讯作者：
Asano, Kenichi
中科院分区：
文献类型：
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作者：
Kikuchi, Kenta;Iida, Mayumi;Asano, Kenichi
巨噬细胞根据其所在的器官表现出不同的表型。此外，他们还可以灵活地转换自己的性格，以适应不断变化的环境。然而，迄今为止，解释巨噬细胞表型转变的分子基础尚未被探索。我们发现，在 C57BL/6J 小鼠体内和体外，CD169(+) 巨噬细胞通过调节转录因子 Maf 的水平来改变其表型。当CD169(+)巨噬细胞暴露于细菌成分时，它们以Maf依赖性方式表达一系列急性炎症反应基因，同时开始下调Maf。这种 Maf 抑制依赖于通过蛋白酶体途径和 microRNA 介导的沉默加速降解。 Maf 的下调在相同的巨噬细胞中解锁了 NF-E2 相关因子 2 主导的细胞保护/抗氧化程序。本研究为以前未解答的问题提供了新的见解，即巨噬细胞如何启动促炎症反应，同时保留其在炎症期间修复受损组织的能力。
Macrophages manifest distinct phenotype according to the organs in which they reside. In addition, they flexibly switch their character in adaptation to the changing environment. However, the molecular basis that explains the conversion of the macrophage phenotype has so far been unexplored. We find that CD169(+) macrophages change their phenotype by regulating the level of a transcription factor Maf both in vitro and in vivo in C57BL/6J mice. When CD169(+) macrophages were exposed to bacterial components, they expressed an array of acute inflammatory response genes in Maf-dependent manner and simultaneously start to downregulate Maf. This Maf suppression is dependent on accelerated degradation through proteasome pathway and microRNA-mediated silencing. The downregulation of Maf unlocks the NF-E2-related factor 2-dominant, cytoprotective/antioxidative program in the same macrophages. The present study provides new insights into the previously unanswered question of how macrophages initiate proinflammatory responses while retaining their capacity to repair injured tissues during inflammation.