The thymus and rheumatology: should we care?

Emilie Cosway, Graham Anderson, Paul Garside, Catriona Prendergast

Research output: Contribution to journalArticlepeer-review

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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.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.

Original languageEnglish
Pages (from-to)189–195
JournalCurrent Opinion in Rheumatology
Volume28
Issue number2
Early online date8 Jan 2016
DOIs
Publication statusPublished - Mar 2016

Keywords

  • dendritic cell
  • T cell
  • thymus
  • tolerance
  • Treg

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