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



Xu, Rong, Shears, Rebecca K, Sharma, Ravi, Krishna, Madhan, Webb, Christopher, Ali, Richard, Wei, Xiaoqing, Kadioglu, Aras ORCID: 0000-0003-1137-6321 and Zhang, Qibo
(2020) IL-35 is critical in suppressing superantigenic <i>Staphylococcus aureus</i>-driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue. MUCOSAL IMMUNOLOGY, 13 (3). pp. 460-470.

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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<sup>+</sup> T cell-mediated immune regulation. This impairment of immune control correlated with a significant downregulation of interleukin-35 (IL-35) expression in tonsillar CD4<sup>+</sup> 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<sup>+</sup> 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
Uncontrolled Keywords: Nasopharynx, Lymphoid Tissue, Lymph Nodes, CD4-Positive T-Lymphocytes, Humans, Staphylococcus aureus, Interleukins, Interleukin-10, Antigens, Bacterial, Superantigens, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Palatine Tonsil, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells
Depositing User: Symplectic Admin
Date Deposited: 13 Jan 2020 11:34
Last Modified: 06 Oct 2023 21:10
DOI: 10.1038/s41385-019-0246-1
Open Access URL: https://doi.org/10.1038/s41385-019-0246-1
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3070461

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