Background Myeloid-derived suppressor cells (MDSCs) are a heterogeneous popuation of myeloid cells that modulate pathogenic response in the autoimmune microenvironment. However, the precise roles of MDSCs in systemic lupus erythematosus (SLE), the prototype autoimmune disease, are not completely understood. Indeed, their immunosuppressive functions in lupus model remain controversial with heterogeneity among MDSCs and differential effects among subpopulations receiving much attention. Programmed death-ligand 1 (PD-L1) is an inhibitory ligand that binds to PD-1 to suppress T cell activation. Multiple studies have explored the potential role of PD-L1 as a mediator of MDSC effects in various cancers. However, the role PD-L1 expression in MDSCs on autoimmune disease is still largely unknown.
Methods In the present study, we investigate the role of PD-L1 expressing MDSC in the MRL/MpJ-Faslpr (MRL-lpr) mouse model.
Results Here we show that the PD-L1 expressing MDSCs express higher amount of immunosuppressive mediators including arginase-1, iNOS and IL-10 than PD-L1 negative MDSCs and exhibit more potent immunoregulatory activity in vitro. We have also identified that in vivo treatment with PD-L1 expressing +MDSC reduced serum autoantibody titres, proteinuria level and mitigated the development of kidney damage. Infusion of PD-L1 expressing MDSCs significantly reduce the double negative T cell population and Tfh cell population in spleens of MRL-lpr mice. Moreover, treatment of PD-L1 expressing MDSCs resulted in an expansion of the regulatory B cell population.
Conclusions Our results indicate PD-L1 expression is critical in MDSCs to maintain MDSC immune regulatory function. Taken together, our results suggest that PD-L1expressing MDSCs may be a potential cell therapeutics for the treatment of autoimmune diseases like SLE.
Funding Source(s): None
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