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Targeting of tolerogenic dendritic cells towards heat‐shock proteins: a novel therapeutic strategy for autoimmune diseases?
Author(s) -
Jansen Ma A. A.,
Spiering Rachel,
Broere Femke,
Laar Jacob M.,
Isaacs John D.,
Eden Willem,
Hilkens Catharien M. U.
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12811
Subject(s) - heat shock protein , immune system , immunology , immune tolerance , arthritis , autoimmunity , rheumatoid arthritis , antigen , autoimmune disease , medicine , antibody , biology , genetics , gene
Summary 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.