Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps

Li Li Shi, Jia Song, Peng Xiong, Ping Ping Cao, Bo Liao, Jin Ma, Ya Na Zhang, Ming Zeng, Yang Liu, Heng Wang, Yong Hua Cui, Shau Ku Huang, Zheng Liu

Research output: Contribution to journalArticle

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Abstract

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-β, 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 eosinophilicCRSwNPsuppressed 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 CRSwNPcould prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume190
Issue number6
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Nasal Polyps
Helper-Inducer T-Lymphocytes
Dendritic Cells
OX40 Ligand
Ligands
Th17 Cells
Th2 Cells
Th1 Cells
Myeloid Cells
T-Lymphocytes
Phenotype
Osteopontin
Transforming Growth Factors
T-Lymphocyte Subsets
Interleukin-12
Coculture Techniques
Reverse Transcriptase Polymerase Chain Reaction

Keywords

  • Eosinophil
  • Osteopontin
  • Phenotype
  • Thymic stromal lymphopoietin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps. / Shi, Li Li; Song, Jia; Xiong, Peng; Cao, Ping Ping; Liao, Bo; Ma, Jin; Zhang, Ya Na; Zeng, Ming; Liu, Yang; Wang, Heng; Cui, Yong Hua; Huang, Shau Ku; Liu, Zheng.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 190, No. 6, 01.01.2014.

Research output: Contribution to journalArticle

Shi, Li Li ; Song, Jia ; Xiong, Peng ; Cao, Ping Ping ; Liao, Bo ; Ma, Jin ; Zhang, Ya Na ; Zeng, Ming ; Liu, Yang ; Wang, Heng ; Cui, Yong Hua ; Huang, Shau Ku ; Liu, Zheng. / Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps. In: American Journal of Respiratory and Critical Care Medicine. 2014 ; Vol. 190, No. 6.
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abstract = "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-β, 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 eosinophilicCRSwNPsuppressed 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 CRSwNPcould prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.",
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AU - Shi, Li Li

AU - Song, Jia

AU - Xiong, Peng

AU - Cao, Ping Ping

AU - Liao, Bo

AU - Ma, Jin

AU - Zhang, Ya Na

AU - Zeng, Ming

AU - Liu, Yang

AU - Wang, Heng

AU - Cui, Yong Hua

AU - Huang, Shau Ku

AU - Liu, Zheng

PY - 2014/1/1

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N2 - 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-β, 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 eosinophilicCRSwNPsuppressed 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 CRSwNPcould prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.

AB - 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-β, 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 eosinophilicCRSwNPsuppressed 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 CRSwNPcould prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.

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KW - Osteopontin

KW - Phenotype

KW - Thymic stromal lymphopoietin

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