title: DC-SIGN promotes allergen uptake and activation of dendritic cells in patients with atopic dermatitis.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a common inflammatory skin disease, concomitant with allergic reactions to allergens. However, the exact mechanisms of allergen-induced immune responses in AD are not clear. The aim of this study is to explore the role of DC-SIGN in capturing and processing glycan-containing allergens and in the subsequent DC activation and T helper cell polarization in AD patients.
  
  
  METHODS
  DC-SIGN expression on DCs from AD patients was analysed by confocal microscopy and flow cytometry. DC-SIGN binding to common allergens was determined by ELISA. Activation of monocyte-derived dendritic cells (Mo-DCs) by allergens was analysed by evaluation of pro-inflammatory cytokines production, and their impact on T-cell responses was investigated by a DC-T cell coculture.
  
  
  RESULTS
  DC-SIGN expression was higher on DCs in the lesional skin of AD patients compared with that of healthy controls and was correlated with disease severity. DC-SIGN could bind to many common allergens including house dust mite allergen (Der p2) and egg white allergen (Gal d2). Mo-DCs showed measurable expression of DC-SIGN and a concentration-dependent uptake of Der p2 and Gal d2, which was inhibited by mannan and anti-DC-SIGN Abs. Der p2 and Gal d2 induced the production of pro-inflammatory cytokines, including TNF-α and IL-6, by DCs from AD patients and facilitated Th2 and Th22 cell polarization.
  
  
  CONCLUSIONS
  Binding of common allergens by DC-SIGN on DCs may initiate allergen sensitization of AD or provoke the relapse of AD. Regulating the allergen-DC-SIGN interaction might be a promising strategy to prevent or intervene in the progress of AD.
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Affiliated Drumtower Hospital of Nanjing University, Nanjing 210008, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Gu
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China. Electronic address: wangbx@ncstdlc.org.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China. Electronic address: dryao_xu@126.com.
authors.forename: X
authors.initials: X
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000378:metabolism*; D039741:Antigens, Dermatophagoides / Q000378:metabolism; D060829:Arthropod Proteins / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism*; D004527:Egg Proteins / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007249:Inflammation; D007378:Interleukins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008875:Middle Aged; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012008:Recurrence; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D055815:Young Adult; D000097043:Interleukin-22; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004527:Egg Proteins; D007378:Interleukins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000097043:Interleukin-22; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C451163:Dermatophagoides pteronyssinus antigen p 2
keywords: Allergen; Atopic dermatitis; DC-SIGN; Dendritic cells