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

• Published in: Immunology 2018-01, Vol.153 (1), p.51-59
• Main Authors: Jansen, Manon A. A., Spiering, Rachel, Broere, Femke, Laar, Jacob M., Isaacs, John D., Eden, Willem, Hilkens, Catharien M. U.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Arthritis; Autoantigens; Autoantigens - immunology; Autoimmune diseases; Autoimmune Diseases - drug therapy; Autoimmune Diseases - etiology; Autoimmune Diseases - metabolism; Autoimmunity; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Heat; Heat shock proteins; Heat-Shock Proteins - immunology; Heat-Shock Proteins - metabolism; Humans; Immune Tolerance; Immunological tolerance; Immunoregulation; Immunotherapy; Inflammation; Lymphocytes; Lymphocytes T; Proteins; regulatory T cells; Review; Rheumatoid arthritis; T cell receptors; Tissues; tolerogenic dendritic cells; Vaccines - administration & dosage; Vaccines - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12811

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. Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. However, it is unknown which autoantigen should be used to load the tolDCs since autoimmune diseases, such as Rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen. We propose that heat shock proteins (HSPs) may be a relevant surrogate antigen, as they are evolutionary conserved between species, ubiquitously expressed in inflamed tissues and have been shown to induce regulatory T cells, ameliorating disease in various arthritis mouse models.