Abstract
T cells play a role in the initiation and perpetuation of tissue inflammation that can lead to tissue destruction. With the discovery of a number of T helper subsets and their potential plasticity during disease it became clear that the T cell behaviour in autoimmune diseases is much more complex than the first Th1/Th2 concept. From experimental autoimmune arthritis models it became clear that the IL-23/IL-17 immune pathway is critical in the development of autoimmune arthritis and IL-17A has been recognized to be a key cytokine involved in initiation and perpetuation of chronic destructive arthritis. Functional studies using T cells and stromal cells from patients with RA revealed improvement of anti-TNF effects when combined with agents neutralizing IL-17A or agents suppressing Th17 cytokines production. Clinic trials will be needed to test whether these data from experimental settings can be translated to human arthritis.
Different approaches are available or under investigation to target: (1) pathogenic T cell activity by inhibiting RORc or STAT3 or the costimulator pathway by CTLA4-Ig; (2) Th17 cytokine production by anti-IL-17A, anti-IL-22, or combination of anti-IL-17A/anti-TNF approaches; (3) Th17 polarization by neutralizing IL-23 using an anti-IL-23 specific antibody, IL-12/IL-23 by an anti-p40 antibody, or the IL-6 signaling pathway; (4) Th17 migration by interfering the CCR6-CCL20 interaction. The challenge is to bring the best to the clinic to further improve current therapy for patients with RA and to reach stable remission or even prevent the development of this disabling disease.
Keywords: T cells, IL-17, Th17, cytokines, transcription factors, arthritis, auto-immune disease, IL-23.
Current Pharmaceutical Design
Title:Role of T Lymphocytes in the Development of Rheumatoid Arthritis. Implications for Treatment
Volume: 21 Issue: 2
Author(s): Erik Lubberts
Affiliation:
Keywords: T cells, IL-17, Th17, cytokines, transcription factors, arthritis, auto-immune disease, IL-23.
Abstract: T cells play a role in the initiation and perpetuation of tissue inflammation that can lead to tissue destruction. With the discovery of a number of T helper subsets and their potential plasticity during disease it became clear that the T cell behaviour in autoimmune diseases is much more complex than the first Th1/Th2 concept. From experimental autoimmune arthritis models it became clear that the IL-23/IL-17 immune pathway is critical in the development of autoimmune arthritis and IL-17A has been recognized to be a key cytokine involved in initiation and perpetuation of chronic destructive arthritis. Functional studies using T cells and stromal cells from patients with RA revealed improvement of anti-TNF effects when combined with agents neutralizing IL-17A or agents suppressing Th17 cytokines production. Clinic trials will be needed to test whether these data from experimental settings can be translated to human arthritis.
Different approaches are available or under investigation to target: (1) pathogenic T cell activity by inhibiting RORc or STAT3 or the costimulator pathway by CTLA4-Ig; (2) Th17 cytokine production by anti-IL-17A, anti-IL-22, or combination of anti-IL-17A/anti-TNF approaches; (3) Th17 polarization by neutralizing IL-23 using an anti-IL-23 specific antibody, IL-12/IL-23 by an anti-p40 antibody, or the IL-6 signaling pathway; (4) Th17 migration by interfering the CCR6-CCL20 interaction. The challenge is to bring the best to the clinic to further improve current therapy for patients with RA and to reach stable remission or even prevent the development of this disabling disease.
Export Options
About this article
Cite this article as:
Lubberts Erik, Role of T Lymphocytes in the Development of Rheumatoid Arthritis. Implications for Treatment, Current Pharmaceutical Design 2015; 21 (2) . https://dx.doi.org/10.2174/1381612820666140825122247
DOI https://dx.doi.org/10.2174/1381612820666140825122247 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
![](/images/wayfinder.jpg)
- 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
-
Mixed Connective Tissue Disease, a Roundabout to Rheumatic Diseases?
Current Rheumatology Reviews n-3 Fatty Acids: Role in Neurogenesis and Neuroplasticity
Current Medicinal Chemistry Cytokine Targeting in Osteoarthritis
Current Drug Targets Cyclooxygenase Inhibitory Natural Products: Current Status
Current Medicinal Chemistry Serum Hepcidin: Its Correlation with Serum Ferritin, Serum Iron and Hemoglobin in Patients of Iron Deficiency Anemia
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Improved Anti-Tumor Activity of Novel Highly Bioactive Liposome-Bound TRAIL in Breast Cancer Cells
Recent Patents on Anti-Cancer Drug Discovery Phytochemical and Biological Activities of five Turanecio Hamzaoglu (Asteraceae) Species from Turkey
Current Enzyme Inhibition Therapeutic Monoclonal Antibodies: Strategies and Challenges for Biosimilars Development
Current Medicinal Chemistry Painful Peripheral Neuropathies
Current Neuropharmacology A Review of Therapeutic Effects of Curcumin
Current Pharmaceutical Design Synthesis of Celecoxib and Structural Analogs- A Review
Current Organic Chemistry Bangladeshi Medicinal Plant Extracts Inhibiting Molecular Interactions between Nuclear Factors and Target DNA Sequences Mimicking NF-kB Binding Sites
Medicinal Chemistry Platelet Function and Antiplatelet Therapy in Cardiovascular Disease: Implications of Genetic Polymorphisms
Current Vascular Pharmacology Parkinson’s Disease: Is there a Role for Dietary and Herbal Supplements?
CNS & Neurological Disorders - Drug Targets Recent Advances in the Development of Anti-Infective Prophylactic and/or Therapeutic Agents Based on Toll-Like Receptor (TLRs)
Recent Patents on Anti-Infective Drug Discovery Inflammation, Sleep, Obesity and Cardiovascular Disease.
Current Vascular Pharmacology Macrophages in Immunopathology of Atherosclerosis: A Target for Diagnostics and Therapy
Current Pharmaceutical Design Plants vs. Cancer: A Review on Natural Phytochemicals in Preventing and Treating Cancers and Their Druggability
Anti-Cancer Agents in Medicinal Chemistry Lymphatics and Inflammation
Current Medicinal Chemistry Evaluation of the <i>In Vivo</i> Acute Toxicity and <i>In Vitro</i> Hemolytic and Immunomodulatory Activities of the <i>Moringa oleifera</i> Flower Trypsin Inhibitor (MoFTI)
Protein & Peptide Letters