ChIP-seq of H3K18la in murine Th17-differentiated T cells
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ABSTRACT: Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. We here demonstrate that extracellular lactate predominantly induces deregulation of the Th17-specific gene expression program by modulating metabolic and epigenetic status of Th17 cells. Following lactate treatment, Th17 cells significantly reduced their IL-17A production and upregulated Foxp3 expression through ROS-driven IL-2 secretion. Moreover, we observed a broad pattern of histone lactylation at various genes in CD4+ T cells, with particularly highly enriched lactylation of histone H3 at the Foxp3 promoter regions in lactate-treated Th17 cells. These results indicate that lactate is capable of reprogramming pro-inflammatory T cell phenotype into regulatory T cells. Moreover, we show that high lactate concentrations suppress the Th17 pathogenicity during intestinal inflammation. Collectively, these findings have a potential therapeutic value for development of novel clinical strategies to target inflammatory and autoimmune diseases.
ORGANISM(S): Mus musculus
PROVIDER: GSE208727 | GEO | 2022/11/25
REPOSITORIES: GEO
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