The thymus and rheumatology: should we care?

Cosway, E., Anderson, G., Garside, P. and Prendergast, C. (2016) The thymus and rheumatology: should we care? Current Opinion in Rheumatology, 28(2), pp. 189-195. (doi: 10.1097/bor.0000000000000251) (PMID:26751840) (PMCID:PMC4732010)

Abstract

Purpose of review: The purpose of this review is to discuss the mechanisms of central and peripheral tolerance in relation to T-cell mediated autoimmunity in rheumatoid arthritis (RA). Recent findings: The well established association between major histocompatibility complex class II and RA has led us to understand that T cells, and the adaptive immune response, are important in the pathogenesis of disease. In order for autoimmune disease to develop, there is a breach of tolerance to self antigen and the mechanisms of both central and peripheral tolerance aim to prevent this. Here, we review evidence from mouse models indicating that alterations in T-cell receptor signalling thresholds during thymic selection may be linked to the escape of T cells that mediate autoimmune arthritis. In addition, we summarize the role of dendritic cells and Foxp3+ regulatory T cells in both peripheral and thymic tolerance, and highlight their relevance to what we know about the aetiology of RA. Summary: Mechanisms of central tolerance in the thymus and peripheral tolerance are in place to control autoreactive T cells and to prevent the development of autoimmune disease. We anticipate that a better understanding of these mechanisms will lead to the development of better, antigen-specific therapeutics to restore tolerance.

• Item Type: Articles
• Additional Information: This work was funded by the ARUK Rheumatoid Arthritis Pathogenesis Centre for Excellence (RACE). G.A. is supported by an MRC Programme Grant; P.G. is supported by an ARUK Programme Grant.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Prendergast, Dr Catriona and Garside, Professor Paul
• Authors: Cosway, E., Anderson, G., Garside, P., and Prendergast, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Current Opinion in Rheumatology
• Publisher: Wolters Kluwer Health
• ISSN: 1040-8711
• ISSN (Online): 1531-6963
• Copyright Holders: Copyright © 2016 Wolters Kluwer Health Inc.
• First Published: First published in Current Opinion in Rheumatology 28(2):189-195
• Publisher Policy: Reproduced under a creative commons license