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

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 (US)
Pages (from-to)387-394.e12
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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