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IL-35 is critical in suppressing superantigenic Staphylococcus aureus-driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2020-01-02 , DOI: 10.1038/s41385-019-0246-1
Rong Xu 1 , Rebecca K Shears 1 , Ravi Sharma 2 , Madhan Krishna 2 , Christopher Webb 3 , Richard Ali 4 , Xiaoqing Wei 4 , Aras Kadioglu 1 , Qibo Zhang 1
Affiliation  

The human nasopharynx is frequently exposed to microbial pathogens, including superantigen-producing Staphylococcus aureus (SAg-Sau), which activates potent pro-inflammatory T cell responses. However, cellular mechanisms that control SAg-Sau-driven T cell activation are poorly understood. Using human nasopharynx-associated lymphoid tissue (NALT), we show that SAg-Sau drove a strong Th17 activation, which was associated with an impaired CD4+ T cell-mediated immune regulation. This impairment of immune control correlated with a significant downregulation of interleukin-35 (IL-35) expression in tonsillar CD4+ T cells by SAg-Sau. Supplementing recombinant IL-35 suppressed SAg-Sau-activated Th17 responses, and this IL-35-mediated suppression positively correlated with the level of Th17 activation. Interestingly, SAg-Sau stimulation induced Foxp3+ Treg expansion and interleukin-10 (IL-10) production, which effectively suppressed the Th1 response, but failed to control the activation of Th17 cells. Overall, our results reveal an aberrant T cell regulation on SAg-Sau-driven Th17 activation and identify IL-35 as a critical cytokine to control superantigenic S.aureus-activated Th17 responses.

中文翻译:

IL-35 对抑制人鼻咽相关淋巴组织中超抗原金黄色葡萄球菌驱动的炎症 Th17 反应至关重要。

人类鼻咽经常暴露于微生物病原体,包括产生超抗原的金黄色葡萄球菌 (SAg-Sau),它会激活有效的促炎 T 细胞反应。然而,人们对控制 SAg-Sau 驱动的 T 细胞激活的细胞机制知之甚少。我们使用人鼻咽相关淋巴组织 (NALT),表明 SAg-Sau 驱动了强烈的 Th17 激活,这与受损的 CD4+ T 细胞介导的免疫调节有关。这种免疫控制受损与 SAg-Sau 对扁桃体 CD4+ T 细胞中白介素 35 (IL-35) 表达的显着下调相关。补充重组 IL-35 抑制了 SAg-Sau 激活的 Th17 反应,并且这种 IL-35 介导的抑制与 Th17 激活水平正相关。有趣的是,SAg-Sau 刺激诱导 Foxp3+ Treg 扩增和白细胞介素 10 (IL-10) 的产生,这有效地抑制了 Th1 反应,但未能控制 Th17 细胞的活化。总体而言,我们的结果揭示了对 SAg-Sau 驱动的 Th17 激活的异常 T 细胞调节,并将 IL-35 鉴定为控制超抗原金黄色葡萄球菌激活的 Th17 反应的关键细胞因子。
更新日期:2020-01-02
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