4.8 Article

Programmed Death-Ligand 1 Expression Potentiates the Immune Modulatory Function Of Myeloid-Derived Suppressor Cells in Systemic Lupus Erythematosus

期刊

FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.606024

关键词

programmed death-ligand 1; myeloid-derived suppressor cells; systemic lupus erythematosus; cell therapy; regulatory B cells

资金

  1. National Research Foundation of Korea (NRF) - Korea government (MSIT) [NRF-2018R1A2A2A05018848]
  2. Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health and Welfare, Republic of Korea [HI20C1496]

向作者/读者索取更多资源

This study found that mRNA levels of immunosuppressive molecules were significantly decreased in MDSCs from lupus patients and mice, while PD-L1 expressing MDSCs from control mice more potently expanded regulatory T cells and regulatory B cells. Therapy with PD-L1 expressing MDSCs reduced autoantibody levels, improved renal pathology in two animal models of lupus, and suppressed pathogenic immune cells. These results suggest that PD-L1 expressing MDSCs could be a promising therapeutic strategy for systemic autoimmune diseases.
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 Roquin(san/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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据