Cord blood granulocytic myeloid-derived suppressor cells impair monocyte T cell stimulatory capacity and response to bacterial stimulation
Cord blood granulocytic myeloid-derived suppressor cells impair monocyte T cell stimulatory capacity and response to bacterial stimulation
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DOI：
10.1038/s41390-019-0504-7
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发表时间：
2019-11-01
影响因子：
3.6
通讯作者：
Koestlin-Gille, Natascha
中科院分区：
文献类型：
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作者：
Dietz, Stefanie;Schwarz, Julian;Koestlin-Gille, Natascha
背景：新生儿败血症是围产期发病率和死亡率的主要原因。与成人相比，新生儿对感染表现出更高的易感性。骨髓源性抑制细胞（MDSC）是对胎儿期积累的其他免疫细胞具有抑制活性并控制新生儿炎症的骨髓细胞。大多数研究MDSC介导的免疫抑制机制的研究都集中在T细胞上。到目前为止，很少有人知道的作用MDSC为monocyte function.METHODS：人脐带血MDSCs（CB-MDSCs）对单核细胞的影响进行了研究，在体外模型。CB-MDSCs与外周血单个核细胞共培养，分析单核细胞表面标志物的表达，T细胞刺激和吞噬能力，以及细胞内细胞因子的产生通过流式cytometer.RESULTS：CB-MDSCs增加了共抑制分子的表达，降低了单核细胞上主要组织相容性复合物II类分子的表达，导致T细胞刺激能力受损。细菌刺激后，吞噬受体的表达，吞噬率和生产的肿瘤坏死因子-a的单核细胞减少CB-MDSCs。结论：我们表明，CB-MDSCs深刻地调节单核细胞的功能，从而间接损害T细胞活化。需要进一步的研究来弄清楚MDSCs是否可以成为新生儿败血症等新生儿炎症性疾病的治疗靶点。
BACKGROUND: Neonatal sepsis is a leading cause of perinatal morbidity and mortality. In comparison to adults, neonates exhibit a higher susceptibility to infections. Myeloid-derived suppressor cells (MDSCs) are myeloid cells with suppressive activity on other immune cells accumulating during foetal life and controlling inflammation in neonates. Most studies investigating the mechanisms for MDSC-mediated immune suppression have been focused on T-cells. Thus far, little is known about the role of MDSC for monocyte function.METHODS: The impact of human cord blood MDSCs (CB-MDSCs) on monocytes was investigated in an in vitro model. CB-MDSCs were co-cultured with peripheral blood mononuclear cells and monocytes were analysed for expression of surface markers, T cell stimulatory and phagocytic capacity, as well as the production of intracellular cytokines by flow cytometry.RESULTS: CB-MDSCs increased the expression of co-inhibitory molecules and decreased the expression of major histocompatibility complex class II molecules on monocytes, leading to an impaired T-cell stimulatory capacity. Upon bacterial stimulation, expression of phagocytosis receptors, phagocytosis rates and production of tumor necrosis factor-a by monocytes was diminished by CB-MDSCs.CONCLUSION: We show that CB-MDSCs profoundly modulate monocyte functions, thereby indirectly impairing T-cell activation. Further research is needed to figure out if MDSCs could be a therapeutic target for inflammatory diseases in neonates like neonatal sepsis.