Searching for the Transcriptomic Signature of Immune Tolerance Induction-Biomarkers of Safety and Functionality for Tolerogenic Dendritic Cells and Regulatory Macrophages.

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.