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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Impact of Antihypertensive Drug Use on Bone Mineral Density and Osteoporotic Fracture - From an Epidemiological Perspective
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Chemical and Biological Aspects of the Genus Verbesina
The Natural Products Journal Aldosterone to Renin Ratio (ARR) in Clinical use, with Reference to the Primary Care Setting: ARR to Whom, When, How, What for?
Current Hypertension Reviews Immunossupressant and Organ Transplantation: Immunophilins Targeting Agent and Alternative Therapies
Current Medicinal Chemistry Toll-Like Receptors and their Role in Renal Pathologies
Inflammation & Allergy - Drug Targets (Discontinued) Are the Long-Acting Intramuscular Formulations of Risperidone or Paliperidone Palmitate Associated with Post-Injection Delirium/Sedation Syndrome? An Assessment of Safety Databases
Current Drug Safety Role of Calcitonin Gene-Related Peptide in Gastric Mucosal Defence and Healing
Current Pharmaceutical Design Pyrrolopyrazoles: Synthesis, Evaluation and Pharmacological Screening as Antidepressant Agents
Medicinal Chemistry 2-Isocyanatobenzonitrile and 2-Isothiocyanatobenzonitrile - Versatile Building Blocks in Organic Synthesis
Current Organic Chemistry Antioxidant Nanoplatforms for Dermal Delivery: Melatonin
Current Drug Metabolism Role of the Peroxynitrite - Poly (ADP-Ribose) Polymerase Pathway in the Pathogenesis of Liver Injury
Current Pharmaceutical Design Lemont B. Kier: A Bibliometric Exploration of his Scientific Production and its Use
Current Computer-Aided Drug Design Amniotic Fluid Embolism: Review
Current Pharmaceutical Biotechnology Relaxin as a Cardiovascular Hormone: Physiology, Pathophysiology and Therapeutic Promises
Cardiovascular & Hematological Agents in Medicinal Chemistry Potential Biomarkers in Diabetic Retinopathy
Current Diabetes Reviews Medical Management of Parkinsons Disease: Focus on Neuroprotection
Current Neuropharmacology Therapeutic Angiogenesis in Ischemic Tissues by Growth Factors and Bone Marrow Mononuclear Cells Administration: Biological Foundation and Clinical Prospects
Current Stem Cell Research & Therapy A Case Report of Necrotizing Fasciitis after Cesarean Delivery
Current Women`s Health Reviews The Impact of Methodology and Confounding Variables on the Association Between Major Depression and Coronary Heart Disease: Review and Recommendations
Current Psychiatry Reviews Comparison of Dapaglifozin and Liraglutide in Patients with Poorly Controlled Type 2 Diabetes Mellitus: a 24-week, Open, Double-centered, Head to Head Trial
Endocrine, Metabolic & Immune Disorders - Drug Targets