Pathogenic T cell subset Th17 is regulated by chromatin remodeling dependent manner to switch Th1 phenotype

Abstract

Abstract In many autoimmune disease such as type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease (IBD), it has been reported that pathogenic Th17 cells exhibit remarkable plasticity to classical Th1 phenotype at the site of autoimmune inflammation. This effecter Th17 cells is also called non-classical Th1 cells because they show the ability to produce IFNγ, similar to conventional Th1 cells, and also continue to produce IL-17 cytokine. The precise mechanism of transcriptional regulation in Th17/IFNγ cells is still not clear yet. By using the splenic naive CD4 T cells, cells were cultured under the Th17 condition including IL-6 and TGFβ for 3 days to 7 days and then cells were added IL-12 to provide Th1-like differentiation condition. In vitro induced Th17 cells were stimulated with anti TCR antibody and assessed the ratio of IL-17 protein production, RORγt and T-bet expression as protein level by flow cytometer. Then, induced Th17 cells were performed to the secondary culture under the several concentration of IL-12 and TGFβ to be able to detect the production of IFNγ, and T-bet. Also we analyzed the specific gene expressions of transcription factor by RT-PCR or quantitative PCR on each day. In this study, we focused on the plasticity of Th17 to Th1 and also compared to the effecter T cell function. We focused on the function of chromatin remodeling in Th17 cells producing both Il-17 and IFNγ by performing ChIP analysis of double producing Th subset and detected that this type plasticity is unique in pathogenic Th17 cell.