CD163+ macrophages infiltration correlates with the immunosuppressive cytokine interleukin 10 expression in tongue leukoplakia
CD163+ macrophages infiltration correlates with the immunosuppressive cytokine interleukin 10 expression in tongue leukoplakia
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DOI：
10.1002/cre2.228
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发表时间：
2019-08-01
影响因子：
1.8
通讯作者：
Yokozaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Shigeoka, Manabu;Koma, Yu-ichiro;Yokozaki, Hiroshi
目的大量证据表明巨噬细胞参与了口腔鳞状细胞癌的免疫编辑过程，但巨噬细胞在口腔癌发生中的作用尚不清楚。我们的目的是阐明巨噬细胞在口腔白斑中的作用，从免疫耐受的角度来看，口腔白斑是最常见的口腔潜在恶性疾病。材料与方法对24例舌白斑患者行手术治疗。评估巨噬细胞标志物与临床病理因素之间的关系。从CD 163（+）人单核细胞白血病细胞系THP-1收获条件培养基。采用定量逆转录-聚合酶链反应和酶联免疫吸附试验对条件培养基处理后人口腔角质形成细胞的表型改变进行了评估。此外，使用免疫组织化学对临床样本进行评价。结果CD 163（+）巨噬细胞高浸润的舌白斑组织与CD 163（+）巨噬细胞低浸润的舌白斑组织相比，其上皮异常增生程度、Ki-67异常表达和细胞角蛋白13丢失程度均显著增高。在体外，CD 163（+）THP-1条件培养基诱导人口腔角质形成细胞产生免疫抑制分子，特别是白细胞介素-10（IL-10）。IL-10表达水平与FOXP 3（+）调节性T细胞和CD 163（+）巨噬细胞数量均呈显著正相关。结论舌白斑组织中CD 163（+）巨噬细胞浸润与免疫抑制细胞因子IL-10表达相关。
Objective Accumulating evidence suggests that macrophages are involved in the immunoediting of oral squamous cell carcinoma but the role of macrophages in oral carcinogenesis is unclear. We aimed to clarify the role of macrophages in oral leukoplakia, which is the most common oral potentially malignant disorder from immunotolerance viewpoint. Materials and methods The study included 24 patients who underwent surgical resection for tongue leukoplakia. The relationships between macrophage markers and clinicopathological factors were assessed. Conditioned medium was harvested from the CD163(+) human monocytic leukaemia cell line, THP-1. The phenotypic alteration of human oral keratinocytes by the conditioned medium treatment was assessed using quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Moreover, the clinical samples were evaluated using immunohistochemistry. Results Tongue leukoplakia tissues with high CD163(+) macrophage infiltration were associated with significantly higher degrees of epithelial dysplasia, abnormal Ki-67 expression and cytokeratin13 loss when compared with the tissues with low CD163(+) macrophage infiltration. In vitro, CD163(+) THP-1 conditioned medium induced immunosuppressive molecules, especially interleukin-10 (IL-10) in human oral keratinocytes. The IL-10 expression levels showed significant positive correlations with not only the numbers of FOXP3(+) regulatory T cells but also that of CD163(+) macrophages. Conclusions In tongue leukoplakia, CD163(+) macrophages infiltration correlates with immunosuppressive cytokine IL-10 expression.