title: Regulatory dendritic cell therapy: from rodents to clinical application.
abstract: Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or "tolerogenic" DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation.
authors: Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: raichregued@upmc.edu.
authors: Dalia
authors: D
authors: Raïch-Regué
authors: Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: 0912720G@student.gla.ac.uk.
authors: Megan
authors: M
authors: Glancy
authors: Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: thomsonaw@upmc.edu.
authors: Angus W
authors: AW
authors: Thomson
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D056747:Immunomodulation; D016219:Immunotherapy, Adoptive; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D057170:Translational Research, Biomedical
keywords: Autoimmunity; Cell therapy; Dendritic cells; Tolerance; Transplantation