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Enhanced Type 2 Immune Reactions by Increased IL-22/IL-22Ra1 Signaling in Chronic Rhinosinusitis With Nasal Polyps

Allergy, Asthma & Immunology Research : AAIR 2020년 12권 6호 p.980 ~ 993
김동규, 조아라, Lim Hee-Suk, 김진엽, 은경미, Oh Ja-Young, 김준곤, 조성호, 김대우,
소속 상세정보
김동규 ( Kim Dong-Kyu ) - Hallym University College of Medicine Hallym University Chuncheon Sacred Heart Hospital Department of Otorhinolaryngology-Head and Neck Surgery
조아라 ( Jo A-Ra ) - University of South Florida Morsani College of Medicine Department of Internal Medicine
 ( Lim Hee-Suk ) - Seoul Metropolitan Government-Seoul National University Boramae Medical Center Department of Otorhinolaryngology-Head and Neck Surgery
김진엽 ( Kim Jin-Youp ) - Seoul Metropolitan Government-Seoul National University Boramae Medical Center Department of Otorhinolaryngology-Head and Neck Surgery
은경미 ( Eun Kyoung-Mi ) - Seoul Metropolitan Government-Seoul National University Boramae Medical Center Department of Otorhinolaryngology-Head and Neck Surgery
 ( Oh Ja-Young ) - Seoul Metropolitan Government-Seoul National University Boramae Medical Center Department of Otorhinolaryngology-Head and Neck Surgery
김준곤 ( Kim Joon-Kon ) - Seoul Metropolitan Government-Seoul National University Boramae Medical Center Department of Otorhinolaryngology-Head and Neck Surgery
조성호 ( Cho Seong-Ho ) - University of South Florida Morsani College of Medicine Department of Internal Medicine
김대우 ( Kim Dae-Woo ) - Seoul Metropolitan Government-Seoul National University Boramae Medical Center Department of Otorhinolaryngology-Head and Neck Surgery

Abstract


Purpose: Recent studies have revealed the pathogenic role of interleukin (IL)-22 in atopic dermatitis and asthma. However, little is known about the role of IL-22 in the pathophysiology of chronic rhinosinusitis with nasal polyps. We aimed to investigate the expression of IL-22 and its pathogenic function in type 2 immune reactions of nasal polyps (NP).

Methods: Protein levels of inflammatory mediators were determined by multiplex immunoassay, and principal component analysis (PCA) was performed. Immunofluorescence analysis and mast cell culture were used to determine the cellular sources of IL-22. Normal human bronchial epithelial (NHBE) cells were stimulated using IL-22 in combination with diverse cytokines, and thymic stromal lymphopoietin (TSLP) was measured.

Results: IL-22 expression was not up-regulated in NP compared with control tissues, but IL-22-high NP revealed distinct features characterized by type 2 inflammatory cytokines such as chemokine (C-C motif) ligand (CCL)-11, CCL-24, and IL-5 on the PCA. Additionally, IL-22 positively correlated with type 2 immune mediators and the disease severity in NP. For the localization of the cellular sources of IL-22 in eosinophilic NP, it was expressed in cells mostly composed of eosinophil peroxidase-positive cells and partially of tryptase-positive cells. The human mast cell line, LAD2 cells, released IL-22 mediated by immunoglobulin E. Moreover, IL-22 receptor subunit alpha-1 (IL-22Ra1) expression was significantly increased in NP. IL-22Ra1 was up-regulated with poly(I:C) stimulation in NHBE cells. Furthermore, TSLP production was enhanced when stimulated with a combination of IL-13, poly(I:C), and IL-22. Treatment with anti-IL-22Ra1 also inhibited IL-22-induced enhancement of TSLP production.

Conclusion: IL-22 was associated with type 2 inflammatory reactions in NP. The IL-22/IL-22Ra1 axis was enhanced and might be involved in type 2 inflammatory reactions via TSLP production in NP.

키워드

Interleukin-22; biomarkers; thymic stromal lymphopoietin; sinusitis; eosinophils; mast cells; nasal polyps; immunoassay; fluorescent antibody technique

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