Heat shock protein 60 reactive T cells in juvenile idiopathic arthritis: what is new?

Yvonne Vercoulen,Nienke H Van Teijlingen,Berent J Prakken,Ismé M De Kleer,Salvatore Albani,Sylvia Kamphuis

doi:10.1186/ar2674

Abstract

Juvenile idiopathic arthritis (JIA) is a disease characterized by chronic joint inflammation, caused by a deregulated immune response. In patients with JIA, heat shock proteins (HSPs) are highly expressed in the synovial lining tissues of inflamed joints. HSPs are endogenous proteins that are expressed upon cellular stress and are able to modulate immune responses. In this review, we concentrate on the role of HSPs, especially HSP60, in modulating immune responses in both experimental and human arthritis, with a focus on JIA. We will mainly discuss the tolerogenic immune responses induced by HSPs, which could have a beneficial effect in JIA. Overall, we will discuss the immune modulatory capacity of HSPs, and the underlying mechanisms of HSP60-mediated immune regulation in JIA, and how this can be translated into therapy.

Highlights

Juvenile idiopathic arthritis (JIA) is an autoimmune disease of unknown cause, characterized by a deregulated immune response in synovial lining tissues of the joints, leading to chronic arthritis in children
We propose that a combination of heat shock proteins (HSPs) peptides signalling through the T cell receptor (TCR) and possibly Toll-like receptors (TLRs) together with pathogenic pattern signalling via TLRs could induce a stronger tolerogenic response (Figure 2c)
In this review we give an overview of the relevance of HSP60, and a few other HSPs, in JIA and immune modulation

Summary

Introduction

Juvenile idiopathic arthritis (JIA) is an autoimmune disease of unknown cause, characterized by a deregulated immune response in synovial lining tissues of the joints, leading to chronic arthritis in children. Cohen and co-workers [32] discovered that some HSP-derived peptides can induce an innate immune response They showed, as discussed before, that HSP60 peptide p277, which was originally identified as a peptide recognized by T cell clones [32], could enhance the population of Tregs. Reactivity to other HSPs is described as well; for example, human homologues of peptides derived from the bacterial HSP dnaJ can induce tolerogenic IL-10 responses in synovial fluid cells of JIA patients [54]. In a phase Ib/II clinical trial, patients suffering from recent-onset type 1 diabetes were treated by subcutaneous injections with epitope p277, the same epitope that enhances Treg function in vitro [61] These patients showed mainly IL-10 production in response to the HSP60 peptide, and clinical improvement was correlated with high IL-10 production before the start of therapy [62]. This local highly inflammatory state needs to be overcome before HSP60-mediated therapy, which may target the Treg population, can be applied,

Conclusion

Matzinger P

46. Wagner-Weiner L

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