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J Immunol. 2018 Jul 15;201(2):635-651. doi: 10.4049/jimmunol.1800040. Epub 2018 Jun 15.

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

Author information

1
Laboratory of Immune Regulation, The School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
2
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
3
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501, Japan.
4
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
5
Department of Research and Development, Kazusa DNA Research Institute, Kisarazu 292-0818, Japan.
6
Division of Biochemistry, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan.
7
Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
8
Laboratory of Oncology, The School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
9
Department of Medical Technology, Faculty of Medicine, Niigata University, Niigata 951-8518, Japan; and.
10
Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
11
Laboratory of Immune Regulation, The School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan; mtanaka@toyaku.ac.jp asanok@toyaku.ac.jp.

Abstract

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.

PMID:
29907708
DOI:
10.4049/jimmunol.1800040

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