Project description:Blood serum and feces samples from a high-cholesterol diet mouse. Extracted with MeOH(100%) and MeOH/H2O 50/50, respectively. Analyzed with a 10 cm Polar C18 column, 20 minutes gradient elution. Internal standard: Sulfamethazine, sulfadimethoxine.
Project description:Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system. The pathogenesis of MS and other autoimmune diseases is defined by a disrupted equilibrium between IL-17A-producing CD4 T cells (Th17) and regulatory CD4 T cells (Treg). The development of Treg and Th17 cells can be regulated by the gut microbiota, however, it is unclear how the gut microbiota is impacted by IL-17A and how this, in turn, modulates Treg and disease. Here, we show that IL-17A deficiency promotes interferon-I-related gene expression and expands gut microbes that induce the Treg cells, resulting in milder disease in a mouse model of MS. Utilizing HLA-DR3.IL17A-/- transgenic mice, we showed significant enrichment of Treg-promoting gut microbes such as Prevotella sp. MGM1, Parabacteroides distasonis and Bacteroides sartorii species. Further, we observed enrichment of bacterial-specific short-chain fatty acid metabolic pathways that promote Treg function in HLA-DR3.IL17A-/- transgenic mice. Notably, disease severity was reversed in IL-17A sufficient mice that received fecal transplants from, and cohoused with, IL-17A-deficient mice, highlighting a critical role for the gut microbiota in inducing Treg and reducing disease severity. Collectively, we show that IL-17A is an important regulator of the gut microbiota-Treg axis, which mediates immune homeostasis, inflammation, and diseases such as MS.
Project description:Blood serum and feces samples from a high-cholesterol diet mouse. Extracted with MeOH(100%) and MeOH/H2O 50/50, respectively. Analyzed with a 10 cm Polar C18 column, 20 minutes gradient elution. Internal standard: Sulfamethazine, sulfadimethoxine.
Project description:This study aims to investigate the DNA methylation patterns at transcription factor binding regions and their evolutionary conservation with respect to binding activity divergence. We combined newly generated bisulfite-sequencing experiments in livers of five mammals (human, macaque, mouse, rat and dog) and matched publicly available ChIP-sequencing data for five transcription factors (CEBPA, HNF4a, CTCF, ONECUT1 and FOXA1). To study the chromatin contexts of TF binding subjected to distinct evolutionary pressures, we integrated publicly available active promoter, active enhancer and primed enhancer calls determined by profiling genome wide patterns of H3K27ac, H3K4me3 and H3K4me1.