Clara cell 10-kDa protein inhibits TH17 responses through modulating dendritic cells in the setting of allergic rhinitis - 30/01/13
Corresponding author: Zheng Liu, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, P.R. China.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.
Le texte complet de cet article est disponible en PDF.Key words : Allergic rhinitis, Clara cell 10-kDa protein, dendritic cell, inhibition, TH17 response
Abbreviations used : AR, CC10, DC, HDM, FITC, FPR2, NLF, OVA, OX40L, PE
Plan
| Supported by National Natural Science Foundation of China (NSFC) grants 81020108018 and 30872847 and the program for New Century Excellent Talents in University from the State Education Ministry grant NCET-07-0326 (to Z.L.), a grant from Ministry of Health of China (201202005), and, in part, National Institutes of Health grants AI052468 and AI073610 (to S.-K.H). |
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| Disclosure of potential conflict of interest: S.-K. Huang has received grants AI052468 and AI073610 from the National Institutes of Health. Z. Liu has received National Natural Science Foundation of China (NSFC) grants 81020108018 and 30872847 and a Program for New Century Excellent Talents in University grant (NCET-07-0326) from the State Education Ministry. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 387 - février 2013 Retour au numéro
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