Transcriptional profiles of intestinal APS & CD4-T cells from control, HFD-induced prediabetic and diabetic mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE52559 | GEO | 2015/11/18
SECONDARY ACCESSION(S): PRJNA229378
REPOSITORIES: GEO
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Project description:To determine whether diet-induced changes in gut microbiota modified intestinal immune cell gene expression, we analyzed the transcriptome of CD4 T lymphocytes isolated from the lamina propria of the small intestine from mice fed with different diets.
2015-11-18 | GSE52558 | GEO
Project description:To determine whether diet-induced changes in gut microbiota modified intestinal immune cell gene expression, we analyzed the transcriptome of antigen presenting cells isolated from the lamina propria of the small intestine of mice fed with different diet.
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Project description:Memory T cells are distinguished from naive T cells by their rapid production of effector cytokines, although mechanisms for this recall response remain undefined. In this study, we investigated transcriptional mechanisms for rapid IFN-? production by Ag-specific memory CD4 T cells. In naive CD4 T cells, IFN-? production only occurred after sustained Ag activation and was associated with high expression of the T-bet transcription factor required for Th1 differentiation and with T-bet binding to the IFN-? promoter as assessed by chromatin immunoprecipitation analysis. By contrast, immediate IFN-? production by Ag-stimulated memory CD4 T cells occurred in the absence of significant nuclear T-bet expression or T-bet engagement on the IFN-? promoter. We identified rapid induction of NF-?B transcriptional activity and increased engagement of NF-?B on the IFN-? promoter at rapid times after TCR stimulation of memory compared with naive CD4 T cells. Moreover, pharmacologic inhibition of NF-?B activity or peptide-mediated inhibition of NF-?B p50 translocation abrogated early memory T cell signaling and TCR-mediated effector function. Our results reveal a molecular mechanism for memory T cell recall through enhanced NF-?B p50 activation and promoter engagement, with important implications for memory T cell modulation in vaccines, autoimmunity, and transplantation.
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Project description:The limited efficacy of current treatment methods and increased type 2 diabetes mellitus (T2DM) incidence constitute an incentive for investigating how metabolic homeostasis is maintained, to improve treatment efficacy and identify novel treatment methods. We analyzed a three-generation family of Chinese origin with the common feature of T2DM attacks and fatty pancreas (FP), alongside 19 unrelated patients with FP and 58 cases with T2DM for genetic variations in Enho, serum adropin, and relative Treg amounts. Functional studies with adropin knockout (AdrKO) in C57BL/6J mice were also performed. It showed serum adropin levels were significantly lower in FP and T2DM patients than in healthy subjects; relative Treg amounts were also significantly decreased in FP and T2DM patients, and positively associated with adropin (r=0.7220, P=0.0001). Sequencing revealed that the patients shared a Cys56Trp mutation in Enho. In vivo, adropin-deficiency was associated with increased severity of glucose homeostasis impairment and fat metabolism disorder. AdrKO mice exhibited reduced endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), impaired glycosphingolipid biosynthesis, adipocytes infiltrating, and loss of Treg, and developed FP and T2DM. Adropin-deficiency contributed to loss of Treg and the development of FP disease and T2DM.
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Project description:BackgroundThe century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity.MethodsWe investigated immune responses in adult individuals pre and 8 months post BCG vaccination. We specifically determined changes in gene expression, cell subset composition, DNA methylome, and the TCR repertoire induced in PBMCs and CD4 memory T cells associated with antigen stimulation by either BCG or a Mycobacterium tuberculosis (Mtb)-derived peptide pool.FindingsFollowing BCG vaccination, we observed increased frequencies of CCR6+ CD4 T cells, which includes both Th1* (CXCR3+CCR6+) and Th17 subsets, and mucosal associated invariant T cells (MAITs). A large number of immune response genes and pathways were upregulated post BCG vaccination with similar patterns observed in both PBMCs and memory CD4 T cells, thus suggesting a substantial role for CD4 T cells in the cellular response to BCG. These upregulated genes and associated pathways were also reflected in the DNA methylome. We described both qualitative and quantitative changes in the BCG-specific TCR repertoire post vaccination, and importantly found evidence for similar TCR repertoires across different subjects.InterpretationThe immune signatures defined herein can be used to track and further characterize immune responses induced by BCG, and can serve as reference for benchmarking novel vaccination strategies.
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Project description:Background:Black pepper or Piper nigrum is a well-known spice, rich in a variety of bioactive compounds, and widely used in many cuisines across the world. In the Indian traditional systems of medicine, it is used to treat gastric and respiratory ailments. The purpose of this investigation is to study the antihyperlipidemic and antiobesity effects of piperonal in high-fat diet (HFD)-induced obese rats. Methods:Piperonal, an active constituent of Piper nigrum seeds, was isolated and confirmed by HPLC, 1H and 13C NMR spectroscopy. Male SD rats were fed on HFD for 22 weeks; Piperonal was supplemented from the 16th week as mentioned in the experimental design. Changes in body weight and body composition were measured by TOBEC, bone mineral composition and density were measured by DXA, and adipose tissue distribution was measured by 7 T-MRI. Plasma levels of glucose, insulin, insulin resistance and lipid profiles of plasma, liver and kidney, adipocyte hormones and liver antioxidants were evaluated using standard kit methods. Expression levels of adipogenic and lipogenic genes, such as PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, HMG-COA and TNF-α were measured by RT-PCR. Histopathological examination of adipose and liver tissues was also carried out in experimental rats. Results:HFD substantially induced body weight, fat%, adipocyte size, circulatory and tissue lipid profiles. It elevated the plasma levels of insulin, insulin resistance and leptin but decreased the levels of adiponectin, BMC and BMD. Increased expression of PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, and TNF-α was noticed in HFD-fed rats. However, supplementation of piperonal (20, 30 and 40 mg/kg b.wt) for 42 days considerably and dose-dependently attenuated the HFD-induced alterations, with the maximum therapeutic activity being noticed at 40 mg/kg b.wt. Conclusions:Piperonal significantly attenuated HFD-induced body weight and biochemical changes through modulation of key lipid metabolizing and obesogenic genes. Our findings demonstrate the efficacy of piperonal as a potent antiobesity agent, provide scientific evidence for its traditional use and suggest the possible mechanism of action.
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