The aryl hydrocarbon receptor/microRNA-212/132 axis in T cells regulates IL-10 production to maintain intestinal homeostasis

Ichino Chinen, Taisuke Nakahama, Akihiro Kimura, Nam T. Nguyen, Hiroshi Takemori, Ayako Kumagai, Hisako Kayama, Kiyoshi Takeda, Soyoung Lee, Hamza Hanieh, Barry Ripley, David Millrine (+5 others)
2015 International Immunology  
Aryl hydrocarbon receptor (Ahr), a transcription factor, plays a critical role in autoimmune inflammation of the intestine. In addition, microRNAs (miRNAs), small non-coding oligonucleotides, mediate pathogenesis of inflammatory bowel diseases (IBD). However, the precise mechanism and interactions of these molecules in IBD pathogenesis have not yet been investigated. We analyzed the role of Ahr and Ahr-regulated miRNAs in colonic inflammation. Our results show that deficiency of Ahr in
more » ... of Ahr in intestinal epithelial cells in mice exacerbated inflammation in dextran sodium sulfate-induced colitis. Deletion of Ahr in T cells attenuated colitis, which was manifested by suppressed T h 17 cell infiltration into the lamina propria. Candidate miRNA analysis showed that induction of colitis elevated expression of the miR-212/132 cluster in the colon of wild-type mice, whereas in Ahr −/− mice, expression was clearly lower. Furthermore, miR-212/132 −/− mice were highly resistant to colitis and had reduced levels of T h 17 cells and elevated levels of IL-10-producing CD4 + cells. In vitro analyses revealed that induction of type 1 regulatory T (Tr1) cells was significantly elevated in miR-212/132 −/− T cells with increased c-Maf expression. Our findings emphasize the vital role of Ahr in intestinal homeostasis and suggest that inhibition of miR-212/132 represents a viable therapeutic strategy for treating colitis. Keywords: aryl hydrocarbon receptor (Ahr), dextran sodium sulfate (DSS)-induced colitis, inflammatory bowel diseases (IBD), microRNA-212/132 (miR-212/132), type 1 regulatory T (Tr1) cells
doi:10.1093/intimm/dxv015 pmid:25862525 fatcat:47unfvjdgngvxlnhxkx4rgfzki