Y Zhang1, Y Luo1, W Li2, J Liu3, M Chen1, H Gu1, B Wang4, X Yao5. 1. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China. 2. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. 3. Department of Dermatology, The Affiliated Drumtower Hospital of Nanjing University, Nanjing 210008, PR China. 4. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China. Electronic address: wangbx@ncstdlc.org. 5. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, PR China. Electronic address: dryao_xu@126.com.
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.
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 ADpatients. METHODS:DC-SIGN expression on DCs from ADpatients 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 ADpatients 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 ADpatients 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: Sanne Duinkerken; Sophie K Horrevorts; Hakan Kalay; Martino Ambrosini; Lisa Rutte; Tanja D de Gruijl; Juan J Garcia-Vallejo; Yvette van Kooyk Journal: Theranostics Date: 2019-08-12 Impact factor: 11.556
Authors: Marit Zuurveld; Nikita P van Witzenburg; Johan Garssen; Gert Folkerts; Bernd Stahl; Belinda Van't Land; Linette E M Willemsen Journal: Front Immunol Date: 2020-05-07 Impact factor: 7.561