Clara cell 10-kDa protein inhibits TH17 responses through modulating dendritic cells in the setting of allergic rhinitis

Yang Liu, Hai Jing Yu, Nan Wang, Ya Na Zhang, Shau Ku Huang, Yong Hua Cui, Zheng Liu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: TH17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. Objective: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on TH17 responses in the setting of AR. Methods: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. TH17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on TH17 cells and CD11c+ dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. Results: Compared with those of control subjects, TH17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced TH17 responses, and CC10 treatment significantly decreased TH17 responses. CC10 had no direct effect on in vitro TH17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-β expression in DCs. Importantly, CC10 was able to inhibit TH17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited TH17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. Conclusion: TH17 responses are enhanced in patients with AR, and CC10 inhibits TH17 responses through modulation of the function of DCs.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number2
DOIs
Publication statusPublished - Feb 1 2013
Externally publishedYes

Fingerprint

Dendritic Cells
Proteins
Th17 Cells
Ovalbumin
Adoptive Transfer
Allergic Rhinitis
OX40 Ligand
Inflammation
Interleukin-23
Nasal Mucosa
Cell Differentiation
Interleukin-6
Flow Cytometry
Cell Culture Techniques
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

Keywords

  • Allergic rhinitis
  • Clara cell 10-kDa protein
  • dendritic cell
  • inhibition
  • T17 response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Clara cell 10-kDa protein inhibits TH17 responses through modulating dendritic cells in the setting of allergic rhinitis. / Liu, Yang; Yu, Hai Jing; Wang, Nan; Zhang, Ya Na; Huang, Shau Ku; Cui, Yong Hua; Liu, Zheng.

In: Journal of Allergy and Clinical Immunology, Vol. 131, No. 2, 01.02.2013.

Research output: Contribution to journalArticle

@article{98b7744b8bbe4c9eb0e833614a59e17d,
title = "Clara cell 10-kDa protein inhibits TH17 responses through modulating dendritic cells in the setting of allergic rhinitis",
abstract = "Background: TH17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. Objective: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on TH17 responses in the setting of AR. Methods: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. TH17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on TH17 cells and CD11c+ dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. Results: Compared with those of control subjects, TH17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced TH17 responses, and CC10 treatment significantly decreased TH17 responses. CC10 had no direct effect on in vitro TH17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-β expression in DCs. Importantly, CC10 was able to inhibit TH17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited TH17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. Conclusion: TH17 responses are enhanced in patients with AR, and CC10 inhibits TH17 responses through modulation of the function of DCs.",
keywords = "Allergic rhinitis, Clara cell 10-kDa protein, dendritic cell, inhibition, T17 response",
author = "Yang Liu and Yu, {Hai Jing} and Nan Wang and Zhang, {Ya Na} and Huang, {Shau Ku} and Cui, {Yong Hua} and Zheng Liu",
year = "2013",
month = "2",
day = "1",
doi = "10.1016/j.jaci.2012.11.027",
language = "English",
volume = "131",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Clara cell 10-kDa protein inhibits TH17 responses through modulating dendritic cells in the setting of allergic rhinitis

AU - Liu, Yang

AU - Yu, Hai Jing

AU - Wang, Nan

AU - Zhang, Ya Na

AU - Huang, Shau Ku

AU - Cui, Yong Hua

AU - Liu, Zheng

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Background: TH17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. Objective: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on TH17 responses in the setting of AR. Methods: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. TH17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on TH17 cells and CD11c+ dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. Results: Compared with those of control subjects, TH17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced TH17 responses, and CC10 treatment significantly decreased TH17 responses. CC10 had no direct effect on in vitro TH17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-β expression in DCs. Importantly, CC10 was able to inhibit TH17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited TH17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. Conclusion: TH17 responses are enhanced in patients with AR, and CC10 inhibits TH17 responses through modulation of the function of DCs.

AB - Background: TH17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. Objective: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on TH17 responses in the setting of AR. Methods: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. TH17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on TH17 cells and CD11c+ dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. Results: Compared with those of control subjects, TH17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced TH17 responses, and CC10 treatment significantly decreased TH17 responses. CC10 had no direct effect on in vitro TH17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-β expression in DCs. Importantly, CC10 was able to inhibit TH17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited TH17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. Conclusion: TH17 responses are enhanced in patients with AR, and CC10 inhibits TH17 responses through modulation of the function of DCs.

KW - Allergic rhinitis

KW - Clara cell 10-kDa protein

KW - dendritic cell

KW - inhibition

KW - T17 response

UR - http://www.scopus.com/inward/record.url?scp=84873413696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873413696&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2012.11.027

DO - 10.1016/j.jaci.2012.11.027

M3 - Article

C2 - 23273949

AN - SCOPUS:84873413696

VL - 131

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 2

ER -