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van Eden W, Jansen MAA, Ludwig I, et al. The Enigma of Heat Shock Proteins in Immune Tolerance. Front Immunol. 2017;8:1599doi: 10.3389/fimmu.2017.01599.
van Eden, W., Jansen, M. A. A., Ludwig, I., van Kooten, P., van der Zee, R., & Broere, F. (2017). The Enigma of Heat Shock Proteins in Immune Tolerance. Frontiers in immunology, 81599. https://doi.org/10.3389/fimmu.2017.01599
van Eden, Willem, et al. "The Enigma of Heat Shock Proteins in Immune Tolerance." Frontiers in immunology vol. 8 (2017): 1599. doi: https://doi.org/10.3389/fimmu.2017.01599
van Eden W, Jansen MAA, Ludwig I, van Kooten P, van der Zee R, Broere F. The Enigma of Heat Shock Proteins in Immune Tolerance. Front Immunol. 2017 Nov 21;8:1599. doi: 10.3389/fimmu.2017.01599. eCollection 2017. PMID: 29209330; PMCID: PMC5702443.
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Front Immunol. 2017 Nov 21;8:1599. doi: 10.3389/fimmu.2017.01599. eCollection 2017.

The Enigma of Heat Shock Proteins in Immune Tolerance.

Frontiers in immunology

Willem van Eden, Manon A A Jansen, Irene Ludwig, Peter van Kooten, Ruurd van der Zee, Femke Broere

Affiliations

  1. Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine (FVM), Utrecht University, Utrecht, Netherlands.

PMID: 29209330 PMCID: PMC5702443 DOI: 10.3389/fimmu.2017.01599

Abstract

The fundamental problem of autoimmune diseases is the failure of the immune system to downregulate its own potentially dangerous cells, which leads to destruction of tissue expressing the relevant autoantigens. Current immunosuppressive therapies offer relief but fail to restore the basic condition of self-tolerance. They do not induce long-term physiological regulation resulting in medication-free disease remissions. Heat shock proteins (HSPs) have shown to possess the capacity of inducing lasting protective immune responses in models of experimental autoimmune diseases. Especially mycobacterial HSP60 and HSP70 were shown to induce disease inhibitory IL-10-producing regulatory T cells in many different models. This in itself may seem enigmatic, since based on earlier studies, HSPs were also coined sometimes as pro-inflammatory damage-associated molecular patterns. First clinical trials with HSPs in rheumatoid arthritis and type I diabetes have also indicated their potential to restore tolerance in autoimmune diseases. Data obtained from the models have suggested three aspects of HSP as being critical for this tolerance promoting potential: 1. evolutionary conservation, 2. most frequent cytosolic/nuclear MHC class II natural ligand source, and 3. upregulation under (inflammatory) stress. The combination of these three aspects, which are each relatively unique for HSP, may provide an explanation for the enigmatic immune tolerance promoting potential of HSP.

Keywords: arthritis; cell stress; heat shock proteins; regulatory T cells; rheumatoid; tolerance mechanisms

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