Inflammation induces bitter taste oversensitization via epigenetic changes in Tas2r gene clusters

T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here, using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly cell type specific and lipopolysaccharide (LPS)-induced inflammation increased the accessibility of many Tas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-term effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments. Overall design: Nucleus preparations from peeled tongue epithelium from the circumvallate papillae of control (PBS) or LPS-treated adult C57BL/6J mice (N=6 mice per group) were used for scATAC-seq analyses.