Clara cell 10-kDa protein inhibits TH 17 responses through modulating dendritic cells in the setting of allergic rhinitis

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 2; pp. 387 - 394.e12
• Main Authors: Liu, Yang, MD, PhD, Yu, Hai-Jing, MD, PhD, Wang, Nan, MD, Zhang, Ya-Na, MD, Huang, Shau-Ku, PhD, Cui, Yong-Hua, MD, Liu, Zheng, MD, PhD
• Format: Journal Article
• Language: English
• Published: 2013
• Subjects: Allergy and Immunology; CC10; Fluorescein isothiocyanate; Ovalbumin; Formyl peptide receptor 2; Clara cell 10-kDa protein; OX40L; inhibition; NLF; House dust mite; FPR2; T H17 response; HDM; AR; FITC; OX40 ligand; PE; Allergic rhinitis; Phycoerythrin; Nasal lavage fluid; OVA; dendritic cell; DC
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.11.027

Background TH 17 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 TH 17 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. TH 17 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 TH 17 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, TH 17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced TH 17 responses, and CC10 treatment significantly decreased TH 17 responses. CC10 had no direct effect on in vitro TH 17 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 TH 17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited TH 17 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 TH 17 responses are enhanced in patients with AR, and CC10 inhibits TH 17 responses through modulation of the function of DCs.