title: Clara cell 10-kDa protein inhibits T(H)17 responses through modulating dendritic cells in the setting of allergic rhinitis.
abstract: BACKGROUND
  T(H)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 T(H)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. T(H)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 T(H)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, T(H)17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced T(H)17 responses, and CC10 treatment significantly decreased T(H)17 responses. CC10 had no direct effect on in vitro T(H)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 T(H)17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited T(H)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.
  
  
  CONCLUSIONS
  T(H)17 responses are enhanced in patients with AR, and CC10 inhibits T(H)17 responses through modulation of the function of DCs.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Yu
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Ya-Na
authors.initials: YN
authors.lastname: Zhang
authors.forename: Shau-Ku
authors.initials: SK
authors.lastname: Huang
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Cui
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D054418:Chemokine CCL20 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D053759:Interleukin-23 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D053278:OX40 Ligand / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology; D044042:Receptors, Formyl Peptide / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014598:Uteroglobin / Q000172:deficiency / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D054418:Chemokine CCL20; D053759:Interleukin-23; D015850:Interleukin-6; D053278:OX40 Ligand; D044042:Receptors, Formyl Peptide; D011994:Recombinant Proteins; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D016212:Transforming Growth Factor beta; D010047:Ovalbumin; D014598:Uteroglobin