The roles of myeloid-derived suppressor cells in transplantation

Abstract

CD11b⁺Gr1⁺ myeloid-derived suppressor cells (MDSCs) are an important regulatory innate cell population and have significant inhibitory effect on T cell-mediated responses. In addition to their negative role in cancer development, MDSCs also exert strong regulatory effects on transplantation and autoimmunity. In many transplantation models, such as bone marrow transplant, renal transplant, heart transplant and skin transplant settings, MDSCs accumulate and have inhibitory effect on graft rejection. However, the inducing factors, detailed phenotype and functional molecular mediators of MDSCs are significantly different in various transplant models. With their strong suppressive activity, MDSCs could become a potential clinical therapy during transplantation tolerance induction and the combination of the MDSCs with other immunoregulatory cells or immunosuppressive drugs is an intriguing protocol in the future. In this review, we will summarize MDSC expansion, activation and induction in different transplantation models and discuss the effects of immunoregulatory cells and immunosuppressive drugs on MDSCs in transplant settings.

Keywords::

• immunosuppressant
• myeloid-derived suppressor cells
• tolerance
• transplantation

Acknowledgements

The authors wish to thank Drs. Chenming Sun and Lina Sun for their kind review of the manuscript.

Financial & competing interests disclosure

Zhao Y was supported by grants from the National Basic Research Program of China (2010CB945301, 2011CB710903), the National Natural Science Foundation for General and Key Programs (C81130055, C81072396), Knowledge Innovation Program of Chinese Academy of Sciences (XDA04020202–19), and the CAS/SAFEA International Partnership Program for Creative Research Teams. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Myeloid-derived suppressor cells (MDSCs) display CD11b⁺Gr1⁺ phenotype, which belongs to a highly heterogeneous cell subpopulation within the innate immune system. MDSCs were roughly divided into two subsets including monocytic-MDSCs and granulocytic-MDSCs.

• Many factors including VEGF, GM-CSF, G-CSF, M-CSF, IFN-γ, IL-1β, IL-6, IL-10, IL-12, IL-13, calcium binding proteins S100A8/S100A9, complement C3 and prostaglandin E2 could induce the expansion and activation of MDSCs.

• The immunosuppressive effects of MDSCs were mediated by many pathways such as iNOS, Arg1, IDO, HO-1 and anti-inflammatory cytokines. MDSCs in different models or its different subpopulations may use distinct inhibitory approaches to downregulate immune response.

• MDSCs are certainly involved in the delayed graft rejection and transplantation immune tolerance induction, which made MDSCs become potential clinical therapy to control the ensuing graft rejection and to establish transplantation tolerance induction. The lack of specific surface markers and the poor understanding on the effector pathways and mechanisms currently limit their application in clinics.