Abstract
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells of myeloid origin with a specific immune inhibitory function that negatively regulates the adaptive immune response. Since MDSC participate in the promotion of tolerance in the context of organ transplantation, therapeutic strategies that regulate the induction and development of MDSC have been the center of scientist attention. Here we review literature regarding induction of MDSC with demonstrated suppressive function among different types of allografts and their mechanism of action. While manipulation of MDSC represents a potential therapeutic approach for the promotion of donor specific tolerance in solid organ transplantation, further characterization of their specific phenotype, which distinguishes MDSC from non-suppressive myeloid cells, and detailed evaluation of the inhibitory mechanism that determines their suppressive function, is necessary for the realistic application of MDSC as biomarkers in health and disease and their potential use as immune cell therapy in organ transplantation.
Highlights
Myelopoiesis is a regular process where the cells of the mononuclear phagocyte system (MPS) originate from common myeloid precursors (CMP) leading to monocytes, macrophages and dendritic cells (DC) under steady state
The results indicate that a gradient of CCL5 between the graft and peripheral blood might contribute to the intra graft localization of Treg in tolerant recipients controlled by Myeloid derived suppressor cells (MDSC)
Using an experimental skin transplant model where bm12 MHC-II minor mismatched graft were transplanted into C57BL/6 recipients, the Horuzsko laboratory demonstrated HLD-G expressing MDSC interacts with immune inhibitory receptors, such as immunoglobulin-like transcript 2 (ILT2), which induces the expansion of MDSC in vivo [57]
Summary
Jordi Ochando 1,2*, Patricia Conde 1,2, Alberto Utrero-Rico 3 and Estela Paz-Artal 3,4. Since MDSC participate in the promotion of tolerance in the context of organ transplantation, therapeutic strategies that regulate the induction and development of MDSC have been the center of scientist attention. We review literature regarding induction of MDSC with demonstrated suppressive function among different types of allografts and their mechanism of action. While manipulation of MDSC represents a potential therapeutic approach for the promotion of donor specific tolerance in solid organ transplantation, further characterization of their specific phenotype, which distinguishes MDSC from non-suppressive myeloid cells, and detailed evaluation of the inhibitory mechanism that determines their suppressive function, is necessary for the realistic application of MDSC as biomarkers in health and disease and their potential use as immune cell therapy in organ transplantation
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