Abstract
Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects largely synovial joints. It has been postulated that activated autoreactive CD4 T cells play a key role in triggering and/or maintaining the chronic inflammatory process in RA. Dendritic cells (DCs) are antigen-presenting cells that activate cognate clonal CD4 T cells in the lymph nodes. The activation process involves the formation of a molecular structure at the DC-CD4 T cell contact zone called immunological synapse (IS). In RA, the synovium, a thin layer of tissue below the capsule in the joints, shows a massive infiltration of DCs and CD4 T cells. Subjects bearing HLA-DRB1 alleles of the Major Histocompatibility Complex II gene displaying a motif called RA “shared epitope (SE)”, have an enhanced susceptibility to suffer RA. Interestingly, the SE-containing HLA-DRB1 molecules display a pocket with a high affinity for citrullinated antigens, which are found at higher levels in subjects prone to develop RA. Thus, it is possible that the DCs of susceptible individuals may form IS with particular features that may present citrullinated peptides to autorreactive naïve CD4 T clones that, after being activated, contribute to the initiation or development of the disease. Herein I put forward a model of RA initiation based on current information on the immune response and RA.
Keywords: Adaptive immune response/ citrullination / shared epitope / immunological synapse
Current Topics in Medicinal Chemistry
Title:Antigen Presentation by Dendritic Cells in Rheumatoid Arthritis
Volume: 13 Issue: 6
Author(s): Jose Luis Rodriguez-Fernandez
Affiliation:
Keywords: Adaptive immune response/ citrullination / shared epitope / immunological synapse
Abstract: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects largely synovial joints. It has been postulated that activated autoreactive CD4 T cells play a key role in triggering and/or maintaining the chronic inflammatory process in RA. Dendritic cells (DCs) are antigen-presenting cells that activate cognate clonal CD4 T cells in the lymph nodes. The activation process involves the formation of a molecular structure at the DC-CD4 T cell contact zone called immunological synapse (IS). In RA, the synovium, a thin layer of tissue below the capsule in the joints, shows a massive infiltration of DCs and CD4 T cells. Subjects bearing HLA-DRB1 alleles of the Major Histocompatibility Complex II gene displaying a motif called RA “shared epitope (SE)”, have an enhanced susceptibility to suffer RA. Interestingly, the SE-containing HLA-DRB1 molecules display a pocket with a high affinity for citrullinated antigens, which are found at higher levels in subjects prone to develop RA. Thus, it is possible that the DCs of susceptible individuals may form IS with particular features that may present citrullinated peptides to autorreactive naïve CD4 T clones that, after being activated, contribute to the initiation or development of the disease. Herein I put forward a model of RA initiation based on current information on the immune response and RA.
Export Options
About this article
Cite this article as:
Rodriguez-Fernandez Jose Luis, Antigen Presentation by Dendritic Cells in Rheumatoid Arthritis, Current Topics in Medicinal Chemistry 2013; 13 (6) . https://dx.doi.org/10.2174/1568026611313060004
DOI https://dx.doi.org/10.2174/1568026611313060004 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Microbiome Regulation of Autoimmune, Gut and Liver Associated Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Myopericarditis, as the First Sign of Rheumatoid Arthritis Relapse, Evaluated by Cardiac Magnetic Resonance
Inflammation & Allergy - Drug Targets (Discontinued) Role of Antioxidants, Essential Fatty Acids, Carnitine, Vitamins, Phytochemicals and Trace Elements in the Treatment of Diabetes Mellitus and its Chronic Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Identification of Novel IRAK-4 Inhibitors Through Pharmacophore Modeling, Atom-based 3D-QSAR, Docking Strategies and Molecular Dynamics Simulation
Letters in Drug Design & Discovery Proteoglycan Involvement in Inflammatory Diseases. New Developments in GAG-Based Therapies
Medicinal Chemistry Reviews - Online (Discontinued) Information of ADME-Associated Proteins and Potential Application for Pharmacogenetic Prediction of Drug Responses
Current Pharmacogenomics The Importance of Integrating SNP and Cheminformatics Resources to Pharmacogenomics
Current Drug Metabolism Endothelial Chemokines in Autoimmune Disease
Current Pharmaceutical Design Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis
Current Pharmaceutical Biotechnology Selenium Donors at the Junction of Inflammatory Diseases
Current Pharmaceutical Design Malignancy Risk in Systemic Lupus: Recent Research and Ongoing Challenges
Current Rheumatology Reviews Role of Sulfonamide Group in Matrix Metalloproteinase Inhibitors
Current Medicinal Chemistry Introduction from Editor-in-Chief
Current Rheumatology Reviews The Structure-Function Relationships of Complement Receptor Type 2 (CR2; CD21)
Current Protein & Peptide Science Recent Patents on Thiazole Derivatives Endowed with Antitumor Activity
Recent Patents on Anti-Cancer Drug Discovery An Evidence-Based Review of the Mechanism of Action, Efficacy, and Safety of Biologic Therapies in the Treatment of Psoriasis and Psoriatic Arthritis
Current Medicinal Chemistry Patent Selections
Recent Patents on Medical Imaging Editorial (Thematic Issue: New Mechanisms and Targets for IBD Therapy: Translational Gastroenterology Comes of Age)
Current Drug Targets NLRP3 Is Involved in Ischemia/Reperfusion Injury
CNS & Neurological Disorders - Drug Targets Synthesis and Antioxidant Activity of Indole Derivatives Containing 4-Substituted Piperazine Moieties
Letters in Drug Design & Discovery