Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR850640_1.fastq.gz | Fastqsanger.gz | |||
| ERR850640_2.fastq.gz | Fastqsanger.gz | |||
| ERR850641_1.fastq.gz | Fastqsanger.gz | |||
| ERR850641_2.fastq.gz | Fastqsanger.gz | |||
| ERR850642_1.fastq.gz | Fastqsanger.gz |
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Project description:CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands
| PRJNA280289 | ENA
Project description:Background: The etiology of Inflammatory Bowel Disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown. Results: Card9 gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptides Reg3 and Reg3 independently of the microbiota. On the other hand, Card9 is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that five weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups' own genotype. Conclusions: These results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners. Card9 genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or healthy microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for the host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders.
2024-05-01 | GSE262585 | GEO
Project description:Cancer immuno-surveillance and response to checkpoint blockade therapy can be affected by multiple environmental factors, including nutrition. However, the direct effects of individual nutrients on anti-tumoral immune responses remain poorly understood. Here we addressed the impact of dietary ligands of Aryl Hydrocarbon receptor (AhR), a transcription factor activated by indoles and tryptophan catabolites generated through food digestion and microbiota metabolism. To this aim, we analyzed pre-clinical tumor models in mice fed on a diet naturally poor in AhR ligands, or the same diet enriched for Indole-3-carbinol, a phytonutrient cleaved by stomach enzymes into AhR agonists.
2025-09-30 | GSE240048 | GEO
Project description:Cancer immuno-surveillance and response to checkpoint blockade therapy can be affected by multiple environmental factors, including nutrition. However, the direct effects of individual nutrients on anti-tumoral immune responses remain poorly understood. Here we addressed the impact of dietary ligands of Aryl Hydrocarbon receptor (AhR), a transcription factor activated by indoles and tryptophan catabolites generated through food digestion and microbiota metabolism. We show that T cells are the direct cellular targets of dietary AhR ligands. Transcriptomic analysis showed that tonic activation of AhR promotes anti-PD1-mediated reinvigoration of progenitor exhausted CD8 T cells by controlling their metabolic fitness, and licences the functional program of effector CD8 T cells.
2025-09-30 | GSE271049 | GEO
Project description:Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor
| PRJNA495640 | ENA
Project description:National screening programs use dried blood specimens to detect abnormal metabolism or aberrant protein function in infants shortly after birth, thus identifying disorders that are not clinically evident in the newborn period. Gut microbiota metabolites and immunological acute phase proteins are capable of revealing potential immune aberrations. Microbial metabolites interact with xenobiotic receptors (i.e., aryl hydrocarbon and pregnane-X) and maintain gastrointestinal tissue health, supported by acute-phase proteins, functioning as sensors of microbial immunomodulation and homeostasis. The delivery mode (vaginal or cesarean section) shapes the microbial colonization, which substantially modulates both the immune system's response and mucosal homeostasis.
This study profiled microbial metabolites of the kynurenine and tryptophan pathway and acute phase proteins in 134 neonatal dried blood specimens. We newly established neonatal blood levels of the aryl hydrocarbon receptor microbial ligands (indole-3-aldehyde, indole-3-butyric acid, and indole-3-acetamide) on the second day of life. Furthermore, we observed divergent microbial metabolic profiles in neonates born vaginally or via cesarean section, hypothesizing potential microbial immunomodulatory influence. In summary, these findings suggest the supportive role of human gut microbiota in developing and maintaining immune system homeostasis.
2022-08-02 | PXD027606 | panorama
Project description:Understanding the mechanisms of host macrophage responses to M. tuberculosis (M.tb.) is essential for uncovering potential avenues of intervention to boost host resistance to infection. Macrophage transcriptome profiling revealed M.tb. infection strongly induced expression of several enzymes controlling tryptophan (Trp) catabolism. This included indole 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2), which catalyze the rate-limiting step in the kynurenine pathway, producing ligands for the aryl hydrocarbon receptor (AHR). The AHR and heterodimeric partners AHR nuclear translocator (ARNT) and RELB are robustly expressed, and AHR and RELB levels further increased during infection. Infection enhanced AHR/ARNT and AHR/RELB DNA binding, and stimulated expression of AHR target genes, including that encoding the inflammatory cytokine IL1beta. AHR target gene expression was further enhanced by exogenous kynurenine, and exogenous Trp, kynurenine or synthetic agonist indirubin reduced mycobacterial viability. Comparative expression profiling revealed that AHR ablation diminished expression of numerous genes implicated in innate immune responses, including several cytokines. Notably, AHR depletion reduced expression of IL23A and IL12B transcripts, which encode subunits of interleukin 23 (IL23), a macrophage cytokine that stimulates production of IL22 by innate lymphoid cells. The AHR directly induced IL23A transcription in human and mouse macrophages through near-upstream enhancer regions. Taken together, these findings show that AHR signaling is strongly engaged in Mtb-infected macrophages, and has widespread effects on innate immune responses. Moreover, they reveal a cascade of AHR-driven innate immune signaling, as IL1B (IL-1β) and IL23 stimulate T cell subsets producing IL22, another direct target of AHR transactivation. Gene expression profiling of Mtb-infected THP-1 monocytic cells following siRNA-mediated Aryl hydrocarbon receptor (AHR) knockdown.
2015-07-14 | E-GEOD-70200 | biostudies-arrayexpress
Project description:Association between Altered Tryptophan Metabolism, Plasma Aryl Hydrocarbon Receptor Agonists, and Inflammatory Chagas Disease
| PRJNA1023247 | ENA
Project description:Aims: Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear. Materials and methods: The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics. Key findings: Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro_x0002_inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice. Significance: These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.
2024-11-04 | GSE280960 | GEO
Project description:Sensing of microbial tryptophan catabolites by the aryl hydrocarbon receptor (AhR) plays a pivotal role in host-microbiome homeostasis by modulating the host immune response. Thereby the involved cellular processes triggered by the metabolites are largely unknown. We analyzed proteomic changes in macrophages trough 24h after treatment with the tryptophan metabolites indole-3-acetic acid (I3AA) or indole-3-aldehyde (IAld), as well as the prototypic AhR-ligand Benzo(a)pyrene (BaP) in the absence and presence of LPS to identify affected processes and pathways.
2021-11-03 | PXD025022 | Pride