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Disease-Specific T-Helper Cell Polarizing Function of Lesional Dendritic Cells in Different Types of Chronic Rhinosinusitis with Nasal Polyps

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Otolaryngol Head & Neck Surg, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Pediat, Wuhan 430030, Peoples R China [3]Natl Hlth Res Inst, Taibei, Taiwan [4]Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol & Allergy, Baltimore, MD 21205 USA
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关键词: eosinophil phenotype thymic stromal lymphopoietin osteopontin

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Rationale: Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear. Objectives: To clarify the phenotypes and Th-cell polarizing functions of dendritic cells (DCs) in different types of CRSwNP. Methods: DC subsets, their surface phenotypes, and Th-cell subsets were studied by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were activated or cultured with autologous naive CD4(+) T cells, and cytokine production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin expression were detected by means of reverse-transcriptase polymerase chain reaction. Measurements and Main Results: Although elevated local Th1 and Th17 cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2 cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs, plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP, but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1) expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL-12, IL-6, and transforming growth factor-beta, and induced increased Th1 and Th17 responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2 responses, but promoted Th1 responses in DC-T cell coculture. Conclusions: Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.

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出版当年[2013]版:
大类 | 1 区 医学
小类 | 1 区 危重病医学 1 区 呼吸系统
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 危重病医学 1 区 呼吸系统
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出版当年[2012]版:
Q1 RESPIRATORY SYSTEM Q1 CRITICAL CARE MEDICINE
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Q1 CRITICAL CARE MEDICINE Q1 RESPIRATORY SYSTEM

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Otolaryngol Head & Neck Surg, Wuhan 430030, Peoples R China
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通讯机构: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Otolaryngol Head & Neck Surg, Wuhan 430030, Peoples R China [*1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Otolaryngol Head & Neck Surg, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
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