Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 15, Pages -Publisher
MDPI
DOI: 10.3390/ijms22157970
Keywords
cell therapy; regulatory myeloid cells; tolerogenic dendritic cells; regulatory macrophages; clinical trials; safety
Funding
- CRTI INSERM
- IMBIO-DC
- Fondation Progreffe
- DHU Oncogreffe
- European Union [FP7-260687, FP7-305147]
- IHU-CESTI (Investissement d'Avenir) [ANR-10-IBHU-005]
- Labex IGO project [ANR-11-LABX-0016-01]
- EU program [H2020-MSCA-ITN-2019 860003]
- IHU-CESTI (Region Pays de la Loire)
- IHU-CESTI (Nantes Metropole)
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Myeloid regulatory cell-based therapy, focusing on generating tolerogenic dendritic cells (tolDCs) and regulatory macrophages (Mregs), has shown great potential in organ transplantation and autoimmune diseases. These cells are produced ex vivo using various differentiation signals and stimuli, with studies in animals and humans leading to clinical trials for therapeutic applications.
Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn's disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). These cells have been extensively studied in animals and humans to develop clinical-grade tolerogenic (tol)DCs. Regulatory macrophages (Mregs) are another type of protective myeloid cell that provide a tolerogenic environment, and have mainly been studied within the context of research on organ transplantation. This review aims to thoroughly describe the ex vivo generation of tolDCs and Mregs, their mechanism of action, as well as their therapeutic application and assessment in human clinical trials.
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