Dendritic cells (DCs) are key regulators of immune responses that operate at the interface between innate and adaptive immunity, and defects in DC functions contribute to the pathogenesis of a variety of disorders. For instance, cancer evolves in the context of limited DC activity, and some autoimmune diseases are initiated by DC-dependent antigen presentation. Thus, correcting aberrant DC functions stands out as a promising therapeutic paradigm for a variety of diseases, as demonstrated by an abundant preclinical and clinical literature accumulating over the past two decades. However, the therapeutic potential of DC-targeting approaches remains to be fully exploited in the clinic. Here, we discuss the unique features of DCs that underlie the high therapeutic potential of DC-targeting strategies and critically analyze the obstacles that have prevented the full realization of this promising paradigm.
- Keywords
- autoimmune disorders, cancer, dendritic cells, immunotherapy, vaccine preparation,
- MeSH
- Antigen-Presenting Cells immunology metabolism MeSH
- Autoimmunity MeSH
- Autoimmune Diseases etiology metabolism therapy MeSH
- Cell Differentiation genetics immunology MeSH
- Dendritic Cells immunology metabolism MeSH
- Immunity * MeSH
- Immune Tolerance * MeSH
- Immunotherapy MeSH
- Humans MeSH
- Cell Communication MeSH
- Disease Susceptibility MeSH
- Neoplasms etiology metabolism pathology therapy MeSH
- Cell Plasticity genetics immunology MeSH
- Antigen Presentation immunology MeSH
- Cancer Vaccines administration & dosage immunology MeSH
- T-Lymphocytes immunology metabolism MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Cancer Vaccines MeSH
Tolerogenic dendritic cells (tolDCs) are explored as a promising standalone or combination therapy in type 1 diabetes (T1D). The therapeutic application of tolDCs, including in human trials, has been tested also in other autoimmune diseases, however, T1D displays some unique features. In addition, unlike in several disease-induced animal models of autoimmune diseases, the prevalent animal model for T1D, the NOD mouse, develops diabetes spontaneously. This review compares evidence of various tolDCs approaches obtained from animal (mainly NOD) models of T1D with a focus on parameters of this cell-based therapy such as protocols of tolDC preparation, antigen-specific vs. unspecific approaches, doses of tolDCs and/or autoantigens, application schemes, application routes, the migration of tolDCs as well as their preventive, early pre-onset intervention or curative effects. This review also discusses perspectives of tolDC therapy and areas of preclinical research that are in need of better clarification in animal models in a quest for effective and optimal tolDC therapies of T1D in humans.
- Keywords
- NOD mouse, animal models, cell therapy, protocol optimization, tolerogenic dendritic cells, type 1 diabetes,
- MeSH
- Dendritic Cells immunology transplantation MeSH
- Diabetes Mellitus, Type 1 immunology MeSH
- Immune Tolerance immunology MeSH
- Disease Models, Animal MeSH
- Mice, Inbred NOD MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH