Immune checkpoint receptors in regulating immune reactivity in rheumatic disease

Immune checkpoint regulators are critical modulators of the immune system, allowing the initiation of a productive immune response and preventing the onset of autoimmunity. Co-inhibitory and co-stimulatory immune checkpoint receptors are required for full T-cell activation and effector functions suc...

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Bibliographic Details
Published in:Arthritis research & therapy 2014-01, Vol.16 (5), p.469-469, Article 469
Main Authors: Ceeraz, Sabrina, Nowak, Elizabeth C, Burns, Christopher M, Noelle, Randolph J
Format: Article
Language:English
Subjects:
Antirheumatic Agents - immunology
Antirheumatic Agents - therapeutic use
Arthritis
Costimulatory and Inhibitory T-Cell Receptors - immunology
Development and progression
Humans
Immune response
Immunity
Inflammation
Inflammation - drug therapy
Inflammation - immunology
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Models, Immunological
Physiological aspects
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
Review
Rheumatic Diseases - drug therapy
Rheumatic Diseases - immunology
Signal Transduction - drug effects
Signal Transduction - immunology
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
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Summary:Immune checkpoint regulators are critical modulators of the immune system, allowing the initiation of a productive immune response and preventing the onset of autoimmunity. Co-inhibitory and co-stimulatory immune checkpoint receptors are required for full T-cell activation and effector functions such as the production of cytokines. In autoimmune rheumatic diseases, impaired tolerance leads to the development of diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjogren's syndrome. Targeting the pathways of the inhibitory immune checkpoint molecules CD152 (cytotoxic T lymphocyte antigen-4) and CD279 (programmed death-1) in cancer shows robust anti-tumor responses and tumor regression. This observation suggests that, in autoimmune diseases, the converse strategy of engaging these molecules may alleviate inflammation owing to the success of abatacept (CD152-Ig) in rheumatoid arthritis patients. We review the preclinical and clinical developments in targeting immune checkpoint regulators in rheumatic disease.
ISSN:1478-6354
1478-6362
1478-6362
1478-6354
DOI:10.1186/s13075-014-0469-1