Interleukin-6 is essential for Staphylococcal exotoxin B-induced T regulatory cell insufficiency in nasal polyps

Authors

  • G. Xu,

    1. Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China,
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  • J. H Xia,

    1. Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China and
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  • H. Zhou,

    1. Department of Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • C. Z. Yu,

    1. Department of Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • Y. Zhang,

    1. Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China and
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  • K. J. Zuo,

    1. Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China,
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  • J. B. Shi,

    1. Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China,
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  • H. B. Li

    1. Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China,
    2. Department of Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Correspondence:
Li Huabin, Allergy and Cancer Center, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, No. 58, Guangzhou 510080, China.
E-mail: allergyli@163.com

Summary

Background The pathogenesis of nasal polyps is still unclear. There is increasing evidence indicating that Staphylococcal aureus (S. aureus) is associated with the formation of nasal polyps, but the mechanism has not been well documented to date.

Methods We stimulated cultured nasal polyps and turbinate tissues with Staphylococcal exotoxin B (SEB), detected the expression of pro-inflammatory cytokines (IL-2, IL-6, and IL-8) and T cell cytokines (IFN-γ, IL-4, IL-5, IL-10, and IL-17) in the supernatants, and evaluated mRNA expression (T-bet, GATA-3, Foxp3, and RORγt) and frequencies of CD4+CD25+ T regulatory cells (Tregs) in nasal tissues. We also evaluated the effects of blocking IL-6 with monoclonal antibodies to T cell profiles in cultured nasal tissues stimulated by SEB.

Results Levels of IL-6, IFN-γ and IL-4 increased significantly in SEB-stimulated nasal polyps. Meanwhile, mRNA expressions of T-bet and GATA-3 were significantly up-regulated, while Foxp3 was inhibited and the frequencies of CD4+CD25+ Tregs were decreased after SEB stimulation. After blocking IL-6, the levels of IL-10 and Foxp3 mRNA, as well as the frequencies of CD4+CD25+ Tregs, were significantly increased, while IFN-γ and IL-4 production and the mRNA expression of T-bet and GATA-3 were significantly inhibited.

Conclusions SEB is able to modulate pro-inflammatory factors, T-helper type 1/Th2 profiles and suppress Treg activity in cultured nasal polyps, which were rescued by blocking IL-6 activity. Therefore, IL-6 is essential for SEB-induced Treg insufficiency in nasal polyps.

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