19:10 - 21:00
Room: Ishikawa Ongakudō Interchange Hall
Poster Session
Phenotypic conversion of the colon CD169+ macrophages by c-Maf.
Kenta Kikuchi, Masato Tanaka, Kenichi Asano
Laboratory of Immune Regulation, The School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

Immune balance of the gastrointestinal tract is orchestrated by heterogenous subsets of innate immune cells. In a previous study, we revealed that gut-resident CD169+ macrophages are involved in exacerbation of DSS-induced colitis in mice. In response to mucosal injury, they produce a chemokine CCL8/MCP-2, which was responsible for the recruitment of inflammatory monocytes. These findings suggested that CD169+ macrophages are attractive targets for the suppression of mucosal injury, however, a genetic program that determines the phenotype of these macrophages remained obscure.

In this study, we identified a transcription factor c-Maf that is highly expressed in the colon and lymph node CD169+ macrophages. By analyzing c-Maf-deficient chimeric mice, we found that c-Maf is dispensable for the development or localization of CD169+ macrophages in the colon, but is essential for expressing acute inflammatory response genes such as CCL8. To our surprise, c-Maf not only promoted acute inflammatory responses but also suppressed some of the downstream targets of Nrf2, a master regulator for oxidative stress responses. When CD169+ macrophages were exposed to stimuli derived from bacterial components, they produced acute inflammatory response genes in c-Maf-dependent manner, and simultaneously downregulated c-Maf. This downregulation of c-Maf was attributable to accelerated degradation through proteasome pathway and miR-129-mediated mRNA silencing. The c-Maf repression induced the Nrf2-dominant cytoprotective phenotype in the same macrophages, represented by upregulation of SLPI and xCT.

Collectively, our study indicate that gut macrophages shift from pro-inflammatory to cytoprotective phenotype by changing c-Maf expression level during inflammation.


Reference:
Mo-P13-32
Session:
Poster Session 13 “Development and function of Macrophage and DC”
Presenter/s:
Kenta Kikuchi
Presentation type:
Poster Presentation
Room:
Ishikawa Ongakudō Interchange Hall
Date:
Monday, 30 October 2017
Time:
19:10 - 21:00
Session times:
19:10 - 21:00