GSE193358
The impact of lactate and indole-3-propionate (IPA) on metabolic and epigenetic state of Th17 cells.
Purpose: Although glycolysis-derived lactate and bacterial product IPA are active metabolites, there is still a lack of understanding of their influence on metabolic and epigentic status of T cells. The aim of this study was to shed light on possible effects of lactate and IPA on function of T cells, including production of cytokines and regulation of trenscriptional factors. Method: Naive mice (8-12-week-old female mice) were sacrificed and CD4+ T cells were purified from spleens and lymph nodes. T lymphocytes were then treated with lactate or IPA for two days. To ensure that gene signatures were derived from T cells and not from contaminating APCs or B cells, T cell isolation kit from Miltenyi Biotec was used (purity over 95 %). Results: The analysis of differential expressed genes of lactate- and IPA-treated Th17 cells revealed multiple effects of extracellular lactate and bacterial IPA on the transcriptional profiles. Lactate induced expression of diverse genes associated with transcriptional signature of regulatory T cells. Conclusion: This study demonstrated that extracellular lactate and microbial metabolite IPA influence transcriptional programs in murine Th17 cells. Overall design: Purifed CD4+ T cells were differentiated under Th17 conditions for 48 hours in the presence or absence of 25 mM sodium lactate and 50 µM IPA, respectively (n= 3 per group).