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Immunology. 2018 Jan;153(1):51-59. doi: 10.1111/imm.12811. Epub 2017 Sep 18.

Targeting of tolerogenic dendritic cells towards heat-shock proteins: a novel therapeutic strategy for autoimmune diseases?

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Division of Immunology, Department of Infectious Diseases and Immunology, Utrecht University, the Netherlands.
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), UK, UK.
NIHR-Newcastle Biomedical Research Centre in Ageing and Long-Term Conditions, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Department of Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht, the Netherlands.


Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T-cell response while leaving other, protective, T-cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen. A possible solution is to use surrogate autoantigens for loading of tolDCs. We propose that heat-shock proteins may be a relevant surrogate antigen, as they are evolutionarily conserved between species, ubiquitously expressed in inflamed tissues and have been shown to induce regulatory T cells, ameliorating disease in various arthritis mouse models. In this review, we provide an overview on how immune tolerance may be restored by tolDCs, the problem of selecting relevant autoantigens for loading of tolDCs, and why heat-shock proteins could be used as surrogate autoantigens.


autoimmune diseases; heat-shock proteins; regulatory T cells; tolerogenic dendritic cells

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