title: Heat shock proteins can be targets of regulatory T cells for therapeutic intervention in rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by excessive immune responses resulting in inflammation of the joints. Although current therapies can be successful in dampening inflammation, a long-lived state of tolerance is seldom achieved. Therefore, novel therapies are needed that restore and maintain tolerance in patients with RA. Targeting regulatory T cells (Tregs) is a successful strategy to achieve tolerance, as was shown in studies performed in animal models and in human clinical trials. The antigen-specificity of Tregs is crucial for their effectiveness and allows for very specific targeting of these cells. However, which antigen is suitable for autoimmune diseases such as RA, for which the autoantigens are largely unknown? Heat shock proteins (HSPs) are ubiquitously expressed and can be up-regulated during inflammation. Additionally, HSPs, or HSP-derived peptides are immunogenic and can be recognised by a variety of immune cells, including Tregs. Therefore, this review highlights the potential of HSP-specific Tregs to control inflammatory immune responses. Targeting HSP-specific Tregs in RA can be achieved via the administration of HSPs (derived peptides), thereby controlling inflammatory responses. This makes HSPs attractive candidates for therapeutic intervention in chronic autoimmune diseases, with the ultimate goal of inducing long-lasting tolerance.
authors.affiliation: Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, the Netherlands.
authors.forename: Martijn J C
authors.initials: MJ
authors.lastname: Van Herwijnen
authors.forename: Ruurd
authors.initials: R
authors.lastname: Van Der Zee
authors.forename: Willem
authors.initials: W
authors.lastname: Van Eden
authors.forename: Femke
authors.initials: F
authors.lastname: Broere
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D010455:Peptides / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D006360:Heat-Shock Proteins; D010455:Peptides