Immunosuppressive effects and mechanisms of three myeloid-derived suppressor cells subsets including monocytic-myeloid-derived suppressor cells, granulocytic-myeloid-derived suppressor cells, and immature-myeloid-derived suppressor cells
Immunosuppressive effects and mechanisms of three myeloid-derived suppressor cells subsets including monocytic-myeloid-derived suppressor cells, granulocytic-myeloid-derived suppressor cells, and immature-myeloid-derived suppressor cells
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DOI：
10.4103/jcrt.jcrt_1222_20
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发表时间：
2021-07-01
影响因子：
1.3
通讯作者：
Minami, Hironobu
中科院分区：
文献类型：
--
作者：
Nagatani, Yoshiaki;Funakoshi, Yohei;Minami, Hironobu
背景：髓源性抑制细胞（MDSC）是髓系免疫细胞的异质群体。最近的报道表明，人MDSC分为三个亚群：单核细胞MDSC（M-MDSC）、粒细胞MDSC（G-MDSC）和未成熟MDSC（I-MDSC）。然而，每个人MDSC子集的特点仍然不清楚。材料和方法：为了评估免疫抑制作用和机制，我们首先进行了T细胞抑制试验，使用从健康供体外周血样本中获得的细胞。测定各MDSC亚群培养上清液中免疫抑制分子的水平，以揭示T细胞抑制机制。然后，我们将这些结果与从癌症患者血液样品中获得的细胞的结果进行了比较。最后，我们调查了健康供体和癌症patients.Results之间的每个MDSC子集的频率的差异：虽然M-MDSC和G-MDSC抑制T细胞活化，I-MDSC没有T细胞抑制作用。我们发现，M-MDSC和G-MDSC的培养上清中分别含有高水平的白细胞介素-1受体拮抗剂（IL-1 RA）和白细胞介素-1酶，在健康供体和癌症患者。I-MDSC培养上清中未检测到抑制分子。在总MDSC的功能MDSC（M-MDSC和G-MDSC）的人口显着增加，在癌症患者与健康的donators.Conclusions相比：虽然M-MDSC和G-MDSC，释放IL-1 RA和IL-1 R α酶，分别抑制T细胞活化，I-MDSC没有免疫抑制作用。与健康供体相比，癌症患者中功能性MDSC的数量增加。
Context: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immune cells of myeloid lineage. Recent reports have suggested that human MDSC are divided into three subsets: monocytic MDSC (M-MDSC), granulocytic MDSC (G-MDSC), and immature MDSC (I-MDSC). However, the characteristics of each human MDSC subset still remain unclear.Materials and Methods: To evaluate the immunosuppressive effects and mechanisms, we first performed a T-cell suppression assay using cells obtained from healthy donor peripheral blood samples. The levels of immune inhibitory molecules in the culture supernatant of each MDSC subset were measured to reveal the T-cell suppressive mechanisms. Then, we compared these results with the results from cells obtained from cancer patient blood samples. Finally, we investigated the difference in the frequency of each MDSC subset between the healthy donors and the cancer patients.Results: Although M-MDSC and G-MDSC suppressed T-cell activation, I-MDSC had no T-cell suppressive effect. We found that the culture supernatant of M-MDSC and G-MDSC contained high levels of interleukin-1 receptor antagonist (IL-1RA) and arginase, respectively, in both healthy donors and cancer patients. No inhibitory molecules were detected in the culture supernatant of I-MDSC. The population of functional MDSC (M-MDSC and G-MDSC) in the total MDSC was significantly increased in cancer patients compared with that in healthy donors.Conclusions: Although M-MDSC and G-MDSC, which released IL-1RA and arginase, respectively, suppressed T-cell activation, I-MDSC did not have an immunosuppressive effect. The population of functional MDSC was increased in cancer patients compared with that in healthy donors.