Macrophages switch their phenotype by regulating maf expression during different phases of inflammation

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

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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. The Journal of Immunology, 2018, 201: 635–651.

Original languageEnglish
Pages (from-to)635-651
Number of pages17
JournalJournal of Immunology
Issue number2
Publication statusPublished - 2018 Jul 15


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