文章：

金黄色葡萄球菌肠毒素在Sézary综合征的肿瘤性T细胞中诱导FOXP3表达

Staphylococcus aureus enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome

原文发布日期：2020-05-14

DOI: 10.1038/s41408-020-0324-3

类型: Article

开放获取: 是

英文摘要：

Sézary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as, Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS.
 

摘要翻译： 

塞扎里综合征（SS）是一种异质性的白血病亚型，属于皮肤T细胞淋巴瘤（CTCL），其特征为全身性红皮病、淋巴结肿大及预后不良。疾病晚期始终伴随严重的免疫失调，多数患者死于微生物（如金黄色葡萄球菌）引起的感染性并发症，而非淋巴瘤本身。本研究探讨了葡萄球菌肠毒素（SE）是否会影响恶性SS细胞的表型，包括调节性T细胞相关标志物FOXP3的表达。通过对原代和培养的恶性细胞进行研究，我们发现当恶性细胞与非恶性细胞共暴露时，SE能诱导恶性细胞表达FOXP3。SE-A（SEA）的MHC II类结合结构域突变可在很大程度上阻断该效应，表明该反应至少部分依赖于MHC II类分子介导的抗原呈递。Transwell实验表明，该效应由可溶性因子诱导，可被抗IL-2抗体部分阻断，且依赖于恶性细胞中的STAT5激活。总体而言，这些发现表明SE通过刺激非恶性细胞来诱导恶性细胞中FOXP3的表达。因此，环境因素（如细菌毒素）暴露的差异可能解释SS恶性细胞中FOXP3表达的异质性。

原文链接：

Staphylococcus aureus enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome