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
-
Effects of Flavonoids in Experimental Models of Arterial Hypertension
Current Topics in Medicinal Chemistry B-Type Natriuretic Peptide for Diagnosis and Therapy
Recent Patents on Cardiovascular Drug Discovery Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases
Current Neuropharmacology Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?
Current Drug Targets The Effect of Antihypertensive Drugs on Central Blood Pressure Beyond Peripheral Blood Pressure. Part II: Evidence for Specific Class-Effects of Antihypertensive Drugs on Pressure Amplification
Current Pharmaceutical Design Interest of α2-Adrenergic Agonists and Antagonists in Clinical Practice: Background, Facts and Perspectives
Current Topics in Medicinal Chemistry Inhibition of Drug Efflux in Mycobacteria with Phenothiazines and Other Putative Efflux Inhibitors
Recent Patents on Anti-Infective Drug Discovery Hypoxia Inducible Factor-1 as a Therapeutic Target in Cerebral Ischemia
Current Signal Transduction Therapy Design, Synthesis, Pharmacological Evaluation and Descriptor Based Similarities Study of N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1- yl]acetamides as Potential Antipsychotics
Medicinal Chemistry The 5-HT1B Receptor: A Novel Target for the Pathophysiology of Depression
Current Drug Targets Cathinone Neurotoxicity (“The “3Ms”)
Current Neuropharmacology The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications
Current Medicinal Chemistry Medications Affecting Functional Status in Older Persons
Current Pharmaceutical Design A Comprehensive Systemic Literature Review of Pericardial Decompression Syndrome: Often Unrecognized and Potentially Fatal Syndrome
Current Cardiology Reviews Postprandial Hypotension - Novel Insights into Pathophysiology and Therapeutic Implications
Current Vascular Pharmacology Interrelationship between Chronic Kidney Disease and Risk of Cardiovascular Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Radiation-Induced Extracranial Carotid Stenosis
Vascular Disease Prevention (Discontinued) Angiotensin-(1-7): Blood, Heart, and Blood Vessels
Current Medicinal Chemistry - Cardiovascular & Hematological Agents The Significance of Endothelium-Derived Hyperpolarizing Factor in the Human Circulation
Current Vascular Pharmacology Dermatological, Cardiovascular and Neurological Morphohistopathological Effects of Fluoropyrimidine-based Chemotherapy in Humans
Clinical Cancer Drugs