Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation

作者：Kikuchi Kenta; Iida Mayumi; Ikeda Naoki; Moriyama Shigetaka; Hamada Michito; Takahashi Satoru; Kitamura Hiroshi; Watanabe Takashi; Hasegawa Yoshinori; Hase Koji; Fukuhara Takeshi; Sato Hideyo; Kobayashi Eri H; Suzuki Takafumi; Yamamoto Masayuki; Tanaka Masato^*; Asano Kenichi^*

来源：The Journal of Immunology, 2018, 201(2): 635-651.

DOI：10.4049/jimmunol.1800040

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.

• 出版日期2018-7-15
• 单位RIKEN