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

Vercoulen Y, van Teijlingen NH, de Kleer IM, Kamphuis S, Albani S, Prakken BJ - Arthritis Res. Ther. (2009)

Bottom Line: HSPs are endogenous proteins that are expressed upon cellular stress and are able to modulate immune responses.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatric Immunology, Wilhelmina Children's hospital, UMCU, Lundlaan 6 3584 EA, Utrecht, The Netherlands. yvercoul@umcutrecht.nl

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.

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HSP60 specific T cells in the synovium of juvenile idiopathic arthritis (JIA) patients are IL-10-producing CD30+ regulatory T cell (Treg)-like cells. (a) HSP60 (stained brown and marked by red arrows) is highly expressed in synovial lining membranes in the inflamed joints of JIA patients. (b) HSP60 is released by the synovial tissues in the inflamed joint. In the synovial fluid, CD4+ T cells are present. T cells that react to the self-HSP60 or HSP60 epitopes produce IL-10 [13,68] and express CD30. Presence of these HSP60-reactive T cells correlates with a mild disease course [13]. Therefore, we hypothesize that these T cells could be CD25- and FOXP3-expressing naturally occurring Tregs [19], or IL-10-producing T regulatory 1 cells. Altogether, HSP60 may induce Tregs in the joints of JIA patients and thereby regulate the inflammation of these JIA patients, as is seen in oligoarticular JIA. HSP, heat shock protein.
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Figure 1: HSP60 specific T cells in the synovium of juvenile idiopathic arthritis (JIA) patients are IL-10-producing CD30+ regulatory T cell (Treg)-like cells. (a) HSP60 (stained brown and marked by red arrows) is highly expressed in synovial lining membranes in the inflamed joints of JIA patients. (b) HSP60 is released by the synovial tissues in the inflamed joint. In the synovial fluid, CD4+ T cells are present. T cells that react to the self-HSP60 or HSP60 epitopes produce IL-10 [13,68] and express CD30. Presence of these HSP60-reactive T cells correlates with a mild disease course [13]. Therefore, we hypothesize that these T cells could be CD25- and FOXP3-expressing naturally occurring Tregs [19], or IL-10-producing T regulatory 1 cells. Altogether, HSP60 may induce Tregs in the joints of JIA patients and thereby regulate the inflammation of these JIA patients, as is seen in oligoarticular JIA. HSP, heat shock protein.

Mentions: Heat shock proteins (HSPs) are endogenous proteins that are expressed upon cellular stress and are able to modulate immune responses. HSPs are highly present at sites of inflammation, like the inflamed joints of JIA patients [3] (Figure 1a).


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

Vercoulen Y, van Teijlingen NH, de Kleer IM, Kamphuis S, Albani S, Prakken BJ - Arthritis Res. Ther. (2009)

HSP60 specific T cells in the synovium of juvenile idiopathic arthritis (JIA) patients are IL-10-producing CD30+ regulatory T cell (Treg)-like cells. (a) HSP60 (stained brown and marked by red arrows) is highly expressed in synovial lining membranes in the inflamed joints of JIA patients. (b) HSP60 is released by the synovial tissues in the inflamed joint. In the synovial fluid, CD4+ T cells are present. T cells that react to the self-HSP60 or HSP60 epitopes produce IL-10 [13,68] and express CD30. Presence of these HSP60-reactive T cells correlates with a mild disease course [13]. Therefore, we hypothesize that these T cells could be CD25- and FOXP3-expressing naturally occurring Tregs [19], or IL-10-producing T regulatory 1 cells. Altogether, HSP60 may induce Tregs in the joints of JIA patients and thereby regulate the inflammation of these JIA patients, as is seen in oligoarticular JIA. HSP, heat shock protein.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2714101&req=5

Figure 1: HSP60 specific T cells in the synovium of juvenile idiopathic arthritis (JIA) patients are IL-10-producing CD30+ regulatory T cell (Treg)-like cells. (a) HSP60 (stained brown and marked by red arrows) is highly expressed in synovial lining membranes in the inflamed joints of JIA patients. (b) HSP60 is released by the synovial tissues in the inflamed joint. In the synovial fluid, CD4+ T cells are present. T cells that react to the self-HSP60 or HSP60 epitopes produce IL-10 [13,68] and express CD30. Presence of these HSP60-reactive T cells correlates with a mild disease course [13]. Therefore, we hypothesize that these T cells could be CD25- and FOXP3-expressing naturally occurring Tregs [19], or IL-10-producing T regulatory 1 cells. Altogether, HSP60 may induce Tregs in the joints of JIA patients and thereby regulate the inflammation of these JIA patients, as is seen in oligoarticular JIA. HSP, heat shock protein.
Mentions: Heat shock proteins (HSPs) are endogenous proteins that are expressed upon cellular stress and are able to modulate immune responses. HSPs are highly present at sites of inflammation, like the inflamed joints of JIA patients [3] (Figure 1a).

Bottom Line: HSPs are endogenous proteins that are expressed upon cellular stress and are able to modulate immune responses.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatric Immunology, Wilhelmina Children's hospital, UMCU, Lundlaan 6 3584 EA, Utrecht, The Netherlands. yvercoul@umcutrecht.nl

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.

Show MeSH
Related in: MedlinePlus