한빛사 논문
Min-Seok Rha MD1,*, Sang-Wook Kim MD, PhD2,3,*, Dong-Yeop Chang MD, PhD1,2,3,*, Jin-Ku Lee MD, PhD4, Jihye Kim DVM, PhD5, Su-Hyung Park PhD1,5, Roza Khamulratova MD, PhD6, Hee-Suk Lim MA7, Kyoung Mi Eun BSc7, Seung-No Hong MD7, Dae Woo Kim MD, PhD7,†, Eui-Cheol Shin MD, PhD1,5,†
1 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
2 Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea
3 Department of Otorhinolaryngology, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea
4 Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Republic of Korea
5 BioMedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
6 Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea
7 Department of Otorhinolaryngology-Head & Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea
Corresponding authors : Dae Woo Kim MD, PhD, Eui-Cheol Shin MD, PhD
*These authors contributed equally to this work.
†These authors contributed equally as senior authors.
Abstract
Background
Staphylococcus aureus enterotoxin (SAE) superantigens are detected in nasal polyps (NPs), and SAE-specific immunoglobulin E predicts asthma comorbidity in patients with NPs. However, roles of SAE superantigens and superantigen-related T-cell responses remain to be elucidated in non-asthmatic patients.
Objective
We investigated the presence of SAEs and SAE-related T cell receptor (TCR) Vβ in non-asthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion.
Methods
Sinonasal tissues were obtained from patients with non-asthmatic chronic rhinosinusitis (CRS) with (CRSwNP) or without NP (CRSsNP) and control subjects. SAE genes were detected by polymerase chain reaction and the TCRVβ distribution and T-cell phenotypes examined by flow cytometry.
Results
Various SAE genes were detected not only in NPs but also in sinonasal tissues of CRSsNP patients and controls. The S. aureus enterotoxin I (SEI) gene was detected in all NPs. The fraction of SEI-responsive TCRVβ+ (TCRVβ1+ and Vβ5.1+) CD4+ T cells was significantly increased only in NPs and ethmoidal mucosal tissues from CRSwNP patients, indicating superantigen-induced expansion. The expanded TCRVβ5.1+ CD4+ T cells expressed proliferation marker Ki-67 and the Th2 transcription factor GATA3. Furthermore, TCRVβ5.1+ CD4+ T cells in NPs highly expressed Th2 markers, including IL-17RB, TSLPR, and CRTH2, with a potent Th2 cytokine-producing ability. Moreover, the expansion of TCRVβ1+ or Vβ5.1+ CD4+ T cells was associated with the Lund-Mackay CT score, indicating disease extent.
Conclusion
In non-asthmatic CRSwNP patients, superantigen-related expansion of CD4+ T cells with Th2 differentiation was associated with the disease extent.
Key words
Chronic rhinosinusitis; nasal polyp; T cells; superantigen; Staphylococcus aureus enterotoxin; Th2
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