DC-SIGN promotes allergen uptake and activation of dendritic cells in patients with atopic dermatitis

Y. Zhang, Y. Luo, W. Li, J. Liu, M. Chen, H. Gu, B. Wang, X. Yao

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)128-136
Number of pages9
JournalJournal of Dermatological Science
Volume84
Issue number2
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Keywords

  • Allergen
  • Atopic dermatitis
  • DC-SIGN
  • Dendritic cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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