Abstract
In humans, T-cell development takes place in the thymus, which contains an external cortical region and an inner medulla. The skeleton of the thymus consists of stromal cells and is filled with thymocytes in different stages of differentiation. Thymocytes undergo to a development process before becoming mature T lymphocytes ready for export to the peripheral lymphoid organs. Classically, T-cell development has been reported to occur in four steps. First, bone marrow derived thymocytes that express neither CD4 nor CD8 surface antigens (double negative [DN] thymocytes) undergo an extensive phase of proliferation and differentiation and begin to express CD4 and CD8 (step 2: double positive [DP] thymocytes). During a subsequent negative selection process, approximately 5% of these DP cells undergo apoptosis. If these cells are not eliminated, they could differentiate into autoreactive lymphocytes, leading to the development of peripheral autoimmune diseases. In the thymus, a particular population of T regulatory (Treg) cells also develops. These Treg cells migrate to the periphery and are capable of suppressing autoreactive lymphocytes that may have escaped from the negative selection process. Autoimmune diseases are generally the result of insufficient negative selection of autoreactive cells in the thymus or a deficiency in Treg cell production or function. Future therapeutic strategies for autoimmune diseases should exploit manipulations in the negative selection process and/or the differentiation of Treg cells in the thymus.
Keywords: Thymus, apoptosis, autoimmunity, negative selection, glucocorticoids, mutant, lymphocytes, corticosteroids, thymectomy, Chemotherapy
Current Pharmaceutical Design
Title: Manipulating Thymic Apoptosis for Future Therapy of Autoimmune Diseases
Volume: 17 Issue: 29
Author(s): Domenico V. Delfino, Nicola Pozzesi, Sara Pierangeli, Emira Ayroldi and Alessandra Fierabracci
Affiliation:
Keywords: Thymus, apoptosis, autoimmunity, negative selection, glucocorticoids, mutant, lymphocytes, corticosteroids, thymectomy, Chemotherapy
Abstract: In humans, T-cell development takes place in the thymus, which contains an external cortical region and an inner medulla. The skeleton of the thymus consists of stromal cells and is filled with thymocytes in different stages of differentiation. Thymocytes undergo to a development process before becoming mature T lymphocytes ready for export to the peripheral lymphoid organs. Classically, T-cell development has been reported to occur in four steps. First, bone marrow derived thymocytes that express neither CD4 nor CD8 surface antigens (double negative [DN] thymocytes) undergo an extensive phase of proliferation and differentiation and begin to express CD4 and CD8 (step 2: double positive [DP] thymocytes). During a subsequent negative selection process, approximately 5% of these DP cells undergo apoptosis. If these cells are not eliminated, they could differentiate into autoreactive lymphocytes, leading to the development of peripheral autoimmune diseases. In the thymus, a particular population of T regulatory (Treg) cells also develops. These Treg cells migrate to the periphery and are capable of suppressing autoreactive lymphocytes that may have escaped from the negative selection process. Autoimmune diseases are generally the result of insufficient negative selection of autoreactive cells in the thymus or a deficiency in Treg cell production or function. Future therapeutic strategies for autoimmune diseases should exploit manipulations in the negative selection process and/or the differentiation of Treg cells in the thymus.
Export Options
About this article
Cite this article as:
V. Delfino Domenico, Pozzesi Nicola, Pierangeli Sara, Ayroldi Emira and Fierabracci Alessandra, Manipulating Thymic Apoptosis for Future Therapy of Autoimmune Diseases, Current Pharmaceutical Design 2011; 17 (29) . https://dx.doi.org/10.2174/138161211798157621
DOI https://dx.doi.org/10.2174/138161211798157621 |
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
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
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Novel Patents Targeting Interleukin-17A; Implications in Cancer and Inflammation
Recent Patents on Anti-Cancer Drug Discovery Azathioprine in Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry The AKT Axis as a Therapeutic Target in Autoimmune Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Therapeutic Use of Vitamin D and its Analogues in Autoimmunity
Recent Patents on Inflammation & Allergy Drug Discovery Nucleic Acids Modulate Autoimmunity Through Nucleic-Acid-Specific Toll-Like Receptors
Current Medicinal Chemistry The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation
Current Diabetes Reviews Imatinib Mesylate: An Innovation in Treatment of Autoimmune Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Use of Synbiotics for Ulcerative Colitis Treatment
Current Clinical Pharmacology Regulatory T Cell Therapy for Type I Diabetes Targeting on β Cell Associated Autoantigens
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Micro- and Nano-particulate Strategies for Antigen Specific Immune Tolerance to Treat Autoimmune Diseases
Pharmaceutical Nanotechnology IL-27: Friend or Foe in the Autoimmune Diseases
Current Immunology Reviews (Discontinued) Editorial [Hot Topic: Genome and Proteome Analyses of Autoimmune Diseases (Executive Editor: G. Neeck)]
Current Pharmaceutical Design Anti-CCP Antibody Detection Facilitates Early Diagnosis and Prognosis of Rheumatoid Arthritis
Current Rheumatology Reviews Glucocorticoids Pharmacology: Past, Present and Future
Current Pharmaceutical Design Current Status and Future Prospects of Small–molecule Protein–protein Interaction (PPI) Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL)
Current Topics in Medicinal Chemistry Control of Interleukin-1β Secretion in Inflammation and Immune Response
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Evidence that Pregnancy Specific Glycoproteins Regulate T-Cell Function and Inflammatory Autoimmune Disease During Pregnancy
Current Drug Targets - Inflammation & Allergy The Use of Citrullinated Peptides for the Diagnosis and Prognosis of Rheumatoid Arthritis
Current Topics in Medicinal Chemistry CCL2-CCR2 Signaling in Disease Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets The Rationale for Comparative Studies of Accelerated Atherosclerosis in Rheumatic Diseases
Current Vascular Pharmacology