A5065656217- Tryptophan and brain disorders
- Immune Cell Function and Interaction
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- Immune cells in cancer
- T-cell and B-cell Immunology
- Bipolar Disorder and Treatment
- Neuroscience and Neuropharmacology Research
- Gut microbiota and health
- Cancer Immunotherapy and Biomarkers
- Polyamine Metabolism and Applications
- Phytochemicals and Antioxidant Activities
- Dyeing and Modifying Textile Fibers
- Circadian rhythm and melatonin
- Pharmacological Effects of Medicinal Plants
- Monoclonal and Polyclonal Antibodies Research
- Skin Protection and Aging
- Receptor Mechanisms and Signaling
- Diet and metabolism studies
- Psoriasis: Treatment and Pathogenesis
- Schizophrenia research and treatment
- Metabolomics and Mass Spectrometry Studies
University of Perugia
2015-2024
National Institutes of Health
2008
Abstract Tryptophan catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan affects responses remain unclear. We provide evidence that short-term, combined effects of deprivation and catabolites result GCN2 kinase-dependent down-regulation TCR ζ-chain murine CD8+ cells. ζ can be demonstrated vivo associated with an impaired cytotoxic function vitro. The longer-term include emergence phenotype naive CD4+CD25− cells via TGF-β...
Highlights•Dendritic cells (DCs) can co-express Arg1 and IDO1 immunosuppressive enzymes•Arg1 activity is required for induction by TGF-β in DCs•Spermidine, a downstream product, but not arginine starvation, induces DCs•Arg1+ myeloid derived suppressor (MDSCs) render DCs via IDO1SummaryArginase 1 (Arg1) indoleamine 2,3-dioxygenase (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine l-tryptophan, respectively, resulting local amino acid deprivation. In addition, unlike...
Despite their common ability to activate intracellular signaling through CD80/CD86 molecules, cytotoxic T lymphocyte antigen 4 (CTLA-4)-Ig and CD28-Ig bias the downstream response in opposite directions, latter promoting immunity, CTLA-4-Ig tolerance, dendritic cells (DCs) with but flexible programs of presentation. Nevertheless, absence suppressor cytokine 3 (SOCS3), CD28-Ig—and associated, dominant IL-6 response—become immunosuppressive mimic effect CTLA-4-Ig, including a high functional...
Abstract Dendritic cell (DC) tryptophan catabolism has emerged in recent years as a major mechanism of peripheral tolerance. However, there are features this mechanism, initiated by IDO, that still unclear, including the role enzymes downstream IDO kynurenine pathway and associated production kynurenines. In study, we provide evidence 1) murine DCs express all necessary for synthesis product breakdown, quinolinate; 2) IFN-γ enhances transcriptional expression these enzymes, although...
Abstract CD8− and CD8+ dendritic cells (DCs) are distinct subsets of mouse splenic accessory with opposite but flexible programs Ag presentation, leading to immunogenic tolerogenic responses, respectively. In this study, we show that the default function DCs relies on autocrine TGF-β, which sustains activation IDO in response environmental stimuli. do not produce yet externally added TGF-β induces turns those from into cells. The acquisition a suppressive phenotype by correlates PI3K/Akt...
We analyzed the contribution of intracellular signaling to functional plasticity dendritic cells (DCs) presenting Candida albicans, a human commensal associated with severe diseases. Distinct pathways were activated by recognition different fungal morphotypes in distinct DC subsets and Peyer's patches DCs. Inflammatory DCs initiated Th17/Th2 responses yeasts through adaptor myeloid differentiation factor-88 (MyD88), whereas tolerogenic activate Th1/T regulatory cell (Treg) programs hyphae...
Tryptophan catabolism occurring in dendritic cells (DCs) and initiated by indoleamine 2,3-dioxygenase (IDO) is an emerging major mechanism of peripheral tolerance. Here we provide evidence that: 1) tryptophan conversion to kynurenines activated DCs cytotoxic T lymphocyte antigen 4, both a soluble form or anchored the regulatory cell (Treg) membrane; 2) increased IDO-dependent tolerogenesis correlates with inhibition DAP12 functions, adapter molecule associated activating receptors; 3)...
Originally predicated on the recognition of an increasing prevalence allergy, hygiene hypothesis was later found to accommodate contrasting epidemiologic trends in developed countries for infectious vs autoimmune diseases. Experimentally, reduced exposure infections will increase risk disease several models experimental autoimmunity. Although TLRs were initially considered as stimulatory molecules capable activating early defense mechanisms against invading pathogens, emerging data suggest...
Significance Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunoregulatory enzyme that transforms tryptophan into kynurenine, endogenous agonist of the aryl hydrocarbon receptor (AhR) whose activation sustains IDO1 expression and activity over long term in dendritic cells (DCs). Here we found N -acetylserotonin (NAS), a metabolite produced along serotonin pathway, acts as positive allosteric modulator (PAM) thus increases kynurenine-mediated AhR DCs. NAS effects on translated protection mice...
A defect in indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for immunoregulatory tryptophan catabolism, impairs development of immune tolerance to autoantigens NOD mice, a model human autoimmune type diabetes (T1D). Whether IDO1 function also defective T1D still unknown. We investigated sera and peripheral blood mononuclear cells (PBMCs) from children with matched controls. These were further included discovery study identify SNPs that might modify the risk T1D. was characterized...
Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first step in kynurenine pathway of tryptophan (Trp) degradation that produces several biologically active Trp metabolites. L-kynurenine (Kyn), byproduct by IDO1, promotes immunoregulatory effects via activation Aryl hydrocarbon Receptor (AhR) dendritic cells (DCs) and T lymphocytes. We here identified nuclear coactivator 7 (NCOA7) as a molecular target 3-hydroxyanthranilic acid (3-HAA), metabolite produced downstream Kyn along pathway. In...
The tryptophan-degrading enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is a plastic immune checkpoint molecule that potently orchestrates responses within the tumor microenvironment (TME). As heme-containing protein, IDO1 catalyzes conversion of essential amino acid tryptophan into immunoactive metabolites, called kynurenines. By depleting and enriching TME with kynurenines, catalytic activity shapes an immunosuppressive TME. Accordingly, inducible or constitutive expression in cancer...
Abstract CTLA-4-Ig and CD28-Ig are both agonist ligands of B7 coreceptor molecules on mouse dendritic cells (DCs), yet they bias the downstream response in opposite directions, promotes tolerance, whereas favors onset immunity. Although engagement by either ligand leads to a mixed cytokine response, dominant IL-6 production prevents IFN-γ-driven induction immunosuppressive tryptophan catabolism mediated IDO. In present study, we show that silencing expression suppressor signaling 3 (SOCS3)...
Abstract The enzyme indoleamine 2,3‐dioxygenase 1 ( IDO 1) catalyses the initial, rate‐limiting step in tryptophan (Trp) degradation, resulting starvation and production of immunoregulatory kynurenines. 1's catalytic function has long been considered as one mechanism responsible for 1‐dependent immune suppression by dendritic cells DC s), which are master regulators balance between immunity tolerance. However, also harbours immunoreceptor tyrosine‐based inhibitory motifs, ITIM 2), that, once...
Abstract Indoleamine 2,3‐dioxygenase ( IDO 1), a tryptophan catabolizing enzyme, is recognized as an authentic regulator of immunity in several physiopathologic conditions. We have recently demonstrated that 1 does not merely degrade and produce immunoregulatory kynurenines, but it also acts signal‐transducing molecule, independently its enzymic function. signalling activity triggered plasmacytoid dendritic cells pDC s) by transforming growth factor‐β TGF ‐β), event requires the...