Abstract
The last years have witnessed a breakthrough in the development of cell-based tolerance-inducing cell therapies for the treatment of autoimmune diseases and solid-organ transplantation. Indeed, the use of tolerogenic dendritic cells (tolDC) and regulatory macrophages (Mreg) is currently being tested in Phase I and Phase II clinical trials worldwide, with the aim of finding an effective therapy able to abrogate the inflammatory processes causing these pathologies without compromising the protective immunity of the patients. However, there exists a wide variety of different protocols to generate human tolDC and Mreg and, consequently, the characteristics of each product are heterogeneous. For this reason, the identification of biomarkers able to define their functionality (tolerogenicity) is of great relevance, on the one hand, to guarantee the safety of tolDC and Mreg before administration and, on the other hand, to compare the results between different cell products and laboratories. In this article, we perform an exhaustive review of protocols generating human tolDC and Mreg in the literature, aiming to elucidate if there are any common transcriptomic signature or potential biomarkers of tolerogenicity among the different approaches. However, and although several effectors seem to be induced in common in some of the most reported protocols to generate both tolDC or Mreg, the transcriptomic profile of these cellular products strongly varies depending on the approach used to generate them.
Highlights
The immune system develops complex and sophisticated reactions, which are able to differentiate between what is dangerous and what is innocuous for the host [1], attacking pathogens and other potentially dangerous antigens while remaining unresponsive against whether non-dangerous or self-molecules
Biomarkers of tolerogenic DC (tolDC) and Mreg cells (DC) and, in a lesser extent, macrophages, which direct the immune response depending on the characteristics of the antigen and the cytokine milieu they encounter [2]
Macrophages play a minor role as antigen-presenting cells (APC), developing some of the regulatory processes mentioned above, their main function consists in the clearance of cell debris, pathogens and other molecules after the immune response has concluded [7]
Summary
The immune system develops complex and sophisticated reactions, which are able to differentiate between what is dangerous and what is innocuous for the host [1], attacking pathogens and other potentially dangerous antigens while remaining unresponsive against whether non-dangerous or self-molecules. This balance between immunogenicity and tolerance is orchestrated in the periphery by professional antigen-presenting cells (APC), such as dendritic. Macrophages play a minor role as APC, developing some of the regulatory processes mentioned above, their main function consists in the clearance of cell debris, pathogens and other molecules after the immune response has concluded [7]
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