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IL-35 is critical in suppressing superantigenic Staphylococcus aureus-driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue

Rong, Xu, Shears, Rebecca K., Sharma, Ravi, Krishna, Madhan, Webb, Christopher, Ali, Richard, Wei, Xiaoqing, Kadioglu, Aras and Zhang, Qibo 2020. IL-35 is critical in suppressing superantigenic Staphylococcus aureus-driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue. Mucosal Immunology 13 , pp. 460-470. 10.1038/s41385-019-0246-1

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Publishing Group
ISSN: 1933-0219
Date of First Compliant Deposit: 9 December 2019
Date of Acceptance: 3 December 2019
Last Modified: 02 Oct 2020 10:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/127412

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