Role of hypoxia-inducible factor-1α expression in regulatory T cells on nasal polypogenesis

Authors

  • Jun Jin MD,

    1. Department of Otorhinolaryngology–Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon, Korea
    2. Department of Otorhinolaryngology, Gyeongsang National University Hospital, Jinju, Korea
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    • Jun Jin, MD, and Dong-Yeop Chang, MD, contributed equally to the completion of this article.

  • Dong-Yeop Chang MD, PhD,

    1. Department of Otorhinolaryngology, Gyeongsang National University Hospital, Jinju, Korea
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    • Jun Jin, MD, and Dong-Yeop Chang, MD, contributed equally to the completion of this article.

  • Sung Ha Kim MD,

    1. Department of Otorhinolaryngology–Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon, Korea
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  • Ki-Sang Rha MD, PhD,

    1. Department of Otorhinolaryngology–Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon, Korea
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  • Ji-Hun Mo MD, PhD,

    1. Department of Otorhinolaryngology–Head and Neck Surgery, Dankook University School of Medicine, Chonan, Korea
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  • Eui-Cheol Shin MD, PhD,

    1. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea
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  • Yong Min Kim MD, PhD

    Corresponding author
    1. Department of Otorhinolaryngology–Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon, Korea
    • Send correspondence to Yong Min Kim, MD, Department of Otorhinolaryngology, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 301-721, Korea. E-mail: entkym@cnu.ac.kr

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  • This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2011-0009790).

  • The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis

Hypoxia-inducible factor-1α (HIF-1α) is considered as a key molecule in regulating Th17:regulatory T-cells (Tregs) balance. The aims of this study were to investigate whether HIF-1α is associated with the RORγ (RAR-related orphan receptor gamma) expression of Tregs in nasal polyps and to verify whether Staphylococcus enterotoxin B (SEB) is involved in this process.

Study Design

Clinical experimental study.

Methods

Forty patients with chronic rhinosinusitis with nasal polyposis were enrolled and divided into eosinophilic nasal polyps (EPs) and noneosinophilic nasal polyps (NEPs) according to the proportion of eosinophils. Fifteen subjects who were undergoing septoplasty were enrolled as control subjects. Expression of HIF-1α in the tissue was measured using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and flow cytometry. The mRNA expression of RORC (RAR-related orphan receptor C) and HIF-1α in Tregs separated from tissues were measured by RT-PCR. Double immunofluorescent staining for RORC/FOXP3 and HIF-1α/FOXP3 were conducted on the tissues. Expression of RORC and HIF-1α in Tregs from peripheral blood mononuclear cells (PBMCs) was measured using flow cytometry after stimulation with SEB.

Results

Expression of RORC and HIF-1α in Tregs was significantly higher in EPs and NEPs compared with control mucosa, and there was a significant correlation between RORC and HIF-1α expression in Tregs. Expression of RORC and HIF-1α mRNA in Tregs separated from the tissues was also significantly higher in nasal polyps compared with control mucosa. Expression of RORC and HIF-1α in Tregs were increased after 24-hour stimulation with SEB in the PBMCs.

Conclusions

HIF-1α–induced RORC expression in Tregs may play a key role in the pathogenesis of nasal polyps.

Level of Evidence

NA Laryngoscope, 124:E151–E159, 2014

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