Abstract
Multiple studies have explored the potential role of programmed death-ligand 1 (PD-L1) as a mediator of Myeloid-derived suppressor cells (MDSCs) effects in various cancers. However, the role PD-L1 expression in MDSCs on autoimmune disease is still largely unknown.This study was undertaken to whether MDSC expressing PD-L1 have more potent immunoregulatory activity and control autoimmunity more effectively in two murine models of lupus (MRL/lpr mice and Roquinsan/san mice). The populations of MDSC were increased in peripheral blood of lupus patients. The mRNA levels of immunosuppressive molecules were profoundly decreased in MDSCs from lupus patients and mice. Co-culture with splenocytes showed that PD-L1 expressing MDSCs from control mice expand both Treg cells and regulatory B cells more potently. Infusion of PD-L1 expressing MDSCs reduced autoantibody levels and degree of proteinuria and improved renal pathology of two animal models of lupus. Moreover, PD-L1 expressing MDSCs therapy can suppress double negative (CD4-CD8-CD3+) T cells, the major pathogenic immune cells and follicular helper T cells in MRL/lpr mice, and podocyte damage. Our results indicate PD-L1 expressing MDSCs have more potent immunoregualtory activity and ameliorate autoimmunity more profoundly. These findings suggest PD-L1 expressing MDSCs be a promising therapeutic strategy targeting systemic autoimmune diseases.
Highlights
Systemic lupus erythematosus (SLE, lupus) is an autoimmune disease characterized by the production of diverse autoantibodies and immune complex deposit in target tissues
In an attempt to test whether programmed death-ligand 1 (PD-L1) positive Myeloid-derived suppressor cells (MDSCs) could be more immunosuppressive, MDSCs were generated from bone marrow cells from C57BL/6 mice as described in Materials and Method section
Myeloid-derived suppressor cells (MDSCs) are a heterogenous collection of myeloid cells composed of myeloid precursors, immature granulocytes, mononuclear macrophages, and dendritic cells
Summary
Systemic lupus erythematosus (SLE, lupus) is an autoimmune disease characterized by the production of diverse autoantibodies and immune complex deposit in target tissues. It affects multiple organs and has significant morbidity and mortality. MDSCs are often generated and expanded under pathologic conditions such as tumor environment or chronic inflammation. They can play an important role because of their potent suppressive roles in the immune response. These cells express immunosuppressive factors such as arginase-1, inducible nitric oxide synthase (iNOS) or reactive oxygen species (ROS), which can induce the inactivation of various immune cells, especially T cells [3]
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