A5033455523- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Bipolar Disorder and Treatment
- Immunotherapy and Immune Responses
- Gut microbiota and health
- Pharmacological Receptor Mechanisms and Effects
- Biochemical Acid Research Studies
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- T-cell and B-cell Immunology
- Autophagy in Disease and Therapy
- Phagocytosis and Immune Regulation
- MicroRNA in disease regulation
- Immune Response and Inflammation
- Biotin and Related Studies
- Neonatal Respiratory Health Research
- RNA regulation and disease
- Circadian rhythm and melatonin
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- Genomics, phytochemicals, and oxidative stress
University of Perugia
2015-2024
Salem Hospital
2019
Heidelberg University
2019
National Institutes of Health
2008
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 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...
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)...
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 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...
Modulation of immune responses is one the main research aims in transplant immunology. In this study, we investigate local immunomodulatory properties soluble CD83 (sCD83) at graft-host interface using high-risk corneal transplantation model. model, which mimics inflammatory status and preexisting vascularization patients undergoing transplantation, allogeneic donor corneas are transplanted onto sCD83-treated recipient animals. This model allows direct precise application modulator side....
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...
Abstract Although human amniotic fluid does contain different populations of foetal‐derived stem cells, scanty information is available on the stemness and potential immunomodulatory activity in vitro expanded, cells. By means a methodology unrequiring immune selection, we isolated characterized cell types from second‐trimester samples (human HASC s). Of those populations, one was by fast doubling time, cells were thus designated as fHASC s. Cells maintained their original phenotype under...
In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of novel class IDO1 inhibitors based on benzimidazole substructure. This family compounds is endowed with an extensive bonding network in protein active site, including interaction pocket C, region not commonly by previously reported inhibitors. The tight packing selected within enzyme contributes strong binding IDO1, inhibitory potency at low...