Microbial metabolite butyrate facilitates M2 macrophage polarization and function.
Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Jian
J
Ji
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Dingming
D
Shu
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Mingzhu
M
Zheng
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Jie
J
Wang
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Chenglong
C
Luo
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Yan
Y
Wang
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Fuyou
F
Guo
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Xian
X
Zou
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Xiaohui
X
Lv
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Ying
Y
Li
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Tianfei
T
Liu
Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.|State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510640, China.
Hao
H
Qu
D000818:Animals; D002087:Butyrates / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects; D005260:Female; D015870:Gene Expression; D006655:Histone Deacetylases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D010641:Phenotype; D050800:STAT6 Transcription Factor / Q000378:metabolism
D002087:Butyrates; D050800:STAT6 Transcription Factor; D016264:Dextran Sulfate; D006655:Histone Deacetylases