Abstract
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.
Highlights
Type 1 diabetes (T1D) is a multifactorial, organ/cell-specific disease resulting from an autoimmune destruction of insulin-producing β cells of the endocrine pancreas by CD4+ and CD8+ T cells, as well as macrophages infiltrating the islets
We have reported stable mouse Tolerogenic dendritic cells (tolDCs) prepared with vitamin D2/dexamethasone and exposed for 24 h to monophosphoryl lipid A (MPLA) [42]
This review is not listing all tolDCs studies in animal models of T1D, but the above described examples well-document that unloaded tolDCs, often without stabilization, or immature Dendritic cells (DCs) were effective in disease prevention, in stopping clinical onset of diabetes at 12 weeks of age or even restoring normoglycaemia in already diabetic non-obese diabetic (NOD) mice
Summary
Type 1 diabetes (T1D) is a multifactorial, organ/cell-specific disease resulting from an autoimmune destruction of insulin-producing β cells of the endocrine pancreas by CD4+ and CD8+ T cells, as well as macrophages infiltrating the islets. This review is not listing all tolDCs studies in animal models of T1D, but the above described examples well-document that unloaded tolDCs, often without stabilization, or immature DCs were effective in disease prevention, in stopping clinical onset of diabetes at 12 weeks of age or even restoring normoglycaemia in already diabetic NOD mice. The induced animal models represent a more challenging scenario for diabetes prevention or treatment and should be included in preclinical optimization of tolDCs. In addition, humanized mouse models were employed to bring testing closer to clinical trials and to assess immune responses in the context of risk human HLA molecules such as HLA-DQ8/RIP-B7.1, or HLA-DR4 transgenic mice [39, 46]. The humanized mouse models bring preclinical optimization of tolDCs one step closer to translation to clinical trials (Figure 1)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
