Myeloid-Derived Suppressor Cells Promote the Progression of Primary Membranous Nephropathy by Enhancing Th17 Response
Myeloid-Derived Suppressor Cells Promote the Progression of Primary Membranous Nephropathy by Enhancing Th17 Response
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骨髓源性抑制细胞通过增强 Th17 反应促进原发性膜性肾病的进展。
DOI：
10.3389/fimmu.2020.01777
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发表时间：
2020-08-20
影响因子：
7.3
通讯作者：
Yi, Huanfa
中科院分区：
文献类型：
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作者：
Li, Huimin;Wu, Hao;Yi, Huanfa
一些研究已经证实髓源性抑制细胞（MDSC）与自身免疫性疾病密切相关，但它们在这些过程中的确切作用仍不清楚。在这里，我们研究了MDSCs在原发性膜性肾病（PMN）患者中的作用。与健康对照（HC）相比，PMN患者外周血中HLA-DR（-）CD11b（+）CD33（+）MDSC的数量显著增加，包括CD14（+）CD66b（-）单核细胞MDSC和CD14（-）CD66b（+）粒细胞MDSC。MDSC的频率与PMN患者血清抗磷脂酶A2受体（抗PLA2R）水平、24小时尿蛋白定量和疾病活动性呈正相关。一致的是，增强的辅助性T细胞2（Th2）和辅助性T细胞17（Th17）的免疫反应与血浆抗PLA2R水平，24小时尿蛋白定量，PMN患者的疾病活动性呈正相关。此外，与HC相比，PMN患者的MDSC在体外以ARG-1依赖的方式表现出显著升高的ARG-1产生和增加的促进Th17分化的潜力。本研究直接证实了MDSC在人PMN中的致病作用，并为PMN的发病机制提供了分子机制。我们的数据表明，MDSCs可能主要通过增强Th17反应来促进PMN疾病进展。因此，MDSC可能是PMN疾病诊断、治疗和预后的重要标志物。
Several studies have confirmed that the myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, but their exact role in these processes remains largely unclear. Here, we investigated the role MDSCs in patients with primary membranous nephropathy (PMN). Compared to healthy controls (HCs), PMN patients showed significantly increased number of HLA-DR(-)CD11b(+)CD33(+)MDSCs in the peripheral blood, including both CD14(+)CD66b(-)monocytic and CD14(-)CD66b(+)granulocytic MDSCs. The frequency of MDSCs was positively correlated with the level of serum anti-phospholipase A2 receptor (anti-PLA2R), 24-h urine protein quantification, and disease activity in PMN patients. Consistently, enhanced T helper 2 (Th2) and T helper 17 (Th17) immune responses were positively associated with plasma anti-PLA2R levels, 24-h urine protein quantification, and the disease activity in PMN patients. Moreover, compared to HCs, MDSCs from PMN patients exhibited significantly elevated arginase-1 (ARG-1) production and increased potential to promote Th17 differentiationin vitroin an ARG-1-dependent manner. This study directly demonstrates a pathogenic role for MDSCs in human PMN and provides a molecular mechanism for the pathogenesis of PMN. Our data show that MDSCs may promote PMN disease progression mainly by enhancing Th17 response. Therefore, MDSCs may be an important diagnostic, therapeutic, and prognostic marker for PMN diseases.