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

Lookup NU author(s): Dr Rachel Spiering, Professor John Isaacs, Dr Catharien Hilkens

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This is the authors' accepted manuscript of a review that has been published in its final definitive form by Blackwell Publishing Ltd, 2018.

For re-use rights please refer to the publisher's terms and conditions.


Abstract

© 2017 John Wiley & Sons Ltd. 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.


Publication metadata

Author(s): Jansen MAA, Spiering R, Broere F, van Laar JM, Isaacs JD, van Eden W, Hilkens CMU

Publication type: Review

Publication status: Published

Journal: Immunology

Year: 2018

Volume: 153

Issue: 1

Pages: 51–59

Print publication date: 01/01/2018

Online publication date: 18/09/2017

Acceptance date: 04/08/2017

ISSN (print): 0019-2805

ISSN (electronic): 1365-2567

Publisher: Blackwell Publishing Ltd

URL: https://doi.org/10.1111/imm.12811

DOI: 10.1111/imm.12811


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