Abstract
The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is now emerging. In particular, IDO1 can either support or antagonize inflammation in a context- and tissuedependent manner. Studies in experimental arthritis have unravelled a previously unappreciated role for IDO in controlling B-cell activation and autoantibody production. IDO dysregulation has been documented in patients with systemic lupus erythematosus, systemic sclerosis and Sjogren’s syndrome, as well as in severe sepsis and chronic kidney disease. This article summarizes the contribution of IDO to the pathophysiology of inflammatory/autoimmune disorders, and discusses whether strategies to restore metabolic equilibrium in the kynurenine pathway might be pursued in diseases states such as rheumatoid arthritis and systemic sclerosis.
Keywords: Autoimmunity, dendritic cell, indoleamine 2, 3-dioxygenase, interferon-γ, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, immune tolerance, regulatory T cell, hematopoietic growth factors, cancer
Current Medicinal Chemistry
Title:Emerging Concepts on Inhibitors of Indoleamine 2,3-Dioxygenase in Rheumatic Diseases
Volume: 19 Issue: 31
Author(s): P. Filippini, N. Del Papa, D. Sambataro, A. Del Bufalo, F. Locatelli and S. Rutella
Affiliation:
Keywords: Autoimmunity, dendritic cell, indoleamine 2, 3-dioxygenase, interferon-γ, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, immune tolerance, regulatory T cell, hematopoietic growth factors, cancer
Abstract: The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is now emerging. In particular, IDO1 can either support or antagonize inflammation in a context- and tissuedependent manner. Studies in experimental arthritis have unravelled a previously unappreciated role for IDO in controlling B-cell activation and autoantibody production. IDO dysregulation has been documented in patients with systemic lupus erythematosus, systemic sclerosis and Sjogren’s syndrome, as well as in severe sepsis and chronic kidney disease. This article summarizes the contribution of IDO to the pathophysiology of inflammatory/autoimmune disorders, and discusses whether strategies to restore metabolic equilibrium in the kynurenine pathway might be pursued in diseases states such as rheumatoid arthritis and systemic sclerosis.
Export Options
About this article
Cite this article as:
Filippini P., Del Papa N., Sambataro D., Del Bufalo A., Locatelli F. and Rutella S., Emerging Concepts on Inhibitors of Indoleamine 2,3-Dioxygenase in Rheumatic Diseases, Current Medicinal Chemistry 2012; 19 (31) . https://dx.doi.org/10.2174/092986712803833353
DOI https://dx.doi.org/10.2174/092986712803833353 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Hypopituitarism in Neurocritical Patients: A Case Report
Endocrine, Metabolic & Immune Disorders - Drug Targets What is the Optimal Treatment for Anemia in Inflammatory Bowel Disease?
Current Drug Delivery Relative Survival Benefit and Morbidity with Fluids in Severe Sepsis - A Network Meta-Analysis of Alternative Therapies
Current Drug Safety Colloidal and Pharmacological Activity of Albumin in Clinical Fluid Management:Recent Developments
Current Drug Therapy A2A Receptor Ligands: Past, Present and Future Trends
Current Topics in Medicinal Chemistry Neuroprotection by the α2-Adrenoceptor Agonist, Dexmedetomidine, in Experimental Stroke Models
Vascular Disease Prevention (Discontinued) Immunotherapy in Bladder Cancer
Current Molecular Pharmacology Cocaine and Acute Vascular Diseases
Current Drug Abuse Reviews Regulation of Adrenomedullin and its Family Peptide by RAMP System – Lessons from Genetically Engineered Mice
Current Protein & Peptide Science Sepsis: The Involvement of Platelets and the Current Treatments
Current Molecular Pharmacology Fluparoxan: A Comprehensive Review of its Discovery, Adrenergic and CNS Activity and Treatment of Cognitive Dysfunction in Central Neurodegenerative Diseases
Mini-Reviews in Medicinal Chemistry Cabazitaxel: A Novel Drug for Hormone-Refractory Prostate Cancer
Mini-Reviews in Medicinal Chemistry The Renin-Angiotensin System: New Insight into Old Therapies
Current Medicinal Chemistry Antisense Therapy for Cardiovascular Diseases
Current Pharmaceutical Design Therapeutical Relevance of MAP-Kinase Inhibitors in Renal Diseases: Current Knowledge and Future Clinical Perspectives
Current Medicinal Chemistry Coumarins as Promising Scaffold for the Treatment of Age-related Diseases – An Overview of the Last Five Years
Current Topics in Medicinal Chemistry Non-Clinical Screening of Cyto-Genotoxicologic Status of Praziquantel Nanoemulsion
Current Bioactive Compounds Pharmacokinetics of Selegiline in a Rabbit Model
Letters in Drug Design & Discovery Context-Dependency of Relations Between Cardiovascular Phenotypes and Genes Involved in Sodium Homeostasis: Findings from the European Project on Genes in Hypertension
Current Hypertension Reviews Cardiotonic Steroids in Adaptation to Dietary Salt Intake
Current Clinical Pharmacology