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
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Origin and Biological Significance of Shed-Membrane Microparticles
Endocrine, Metabolic & Immune Disorders - Drug Targets A Review of the ADAMTS Family, Pharmaceutical Targets of the Future
Current Pharmaceutical Design Apolipoprotein E Gene Variants of Alzheimer's Disease and Vascular Dementia Patients in a Community Population of Nanking
Medicinal Chemistry Sonoanatomy and Sonopathology of Complex Anatomic Areas
Current Rheumatology Reviews Identification of a Linear Epitope Recognized by a Monoclonal Antibody Directed to the Heterogeneous Nucleoriboprotein A2
Protein & Peptide Letters Editorial [Hot topic: Thrombospondins (Guest Editor: Jack Lawler)]
Current Drug Targets Cyclin-Dependent Kinase Inhibition by Flavoalkaloids
Mini-Reviews in Medicinal Chemistry Vaccination and Rheumatic Diseases: Is There Still a Dilemma?
Current Rheumatology Reviews Ambiguities in Neutrophil Extracellular Traps. Ongoing Concepts and Potential Biomarkers for Rheumatoid Arthritis: A Narrative Review
Current Rheumatology Reviews Calcineurin Inhibition and Development: Insights from Research Models
Current Enzyme Inhibition CTLA-4Ig: Uses and Future Directions
Recent Patents on Inflammation & Allergy Drug Discovery Antibodies Against Complement System in SLE and their Potential Diagnostic Utility
Current Rheumatology Reviews A Quantitative Structure-Activity Relationship Study on Some Novel Series of Hydroxamic Acid Analogs Acting as Matrix Metalloproteinase Inhibitors
Medicinal Chemistry Immunohistochemical Expression of Vascular Endothelial Growth Factor (VEGF) and its Possible Role in Tumour Progression During Malignant Transformation of Atrophic Epithelium in Oral Submucous Fibrosis
Current Angiogenesis (Discontinued) The Relationship Between Prolidase Activity and Atrial Electromechanical Changes in Patients with Paroxysmal Atrial Fibrillation
Combinatorial Chemistry & High Throughput Screening Rapid Analysis of Pharmacology for Infectious Diseases
Current Topics in Medicinal Chemistry The 2010 Patent Landscape for Spleen Tyrosine Kinase Inhibitors+
Recent Patents on Inflammation & Allergy Drug Discovery Methotrexate in the Treatment of Psoriasis and Rheumatoid Arthritis: Mechanistic Insights, Current Issues and Novel Delivery Approaches
Current Pharmaceutical Design Editorial (Hot Topic: Wrist Arthritis-The Hand Surgeon’s Perspective)
Current Rheumatology Reviews Controlled Release Gel Encompassing Curcumin Microspheres and Diclofenac Diethylamine for Feat Against Arthritis Inflammation
Current Rheumatology Reviews