Abstract
Dendritic cells (DCs) have been shown to play a key role in the initiation and maintenance of immune responses to microbial pathogens as well as to allergens, but the exact mechanisms of their involvement in allergic responses and Th2 cell differentiation have remained elusive. Using retagging, we identified DC-SIGN as a novel receptor involved in the initial recognition and uptake of the major house dust mite and dog allergens Der p 1 and Can f 1, respectively. To confirm this, we used gene silencing to specifically inhibit DC-SIGN expression by DCs followed by allergen uptake studies. Binding and uptake of Der p 1 and Can f 1 allergens was assessed by ELISA and flow cytometry. Intriguingly, our data showed that silencing DC-SIGN on DCs promotes a Th2 phenotype in DC/T cell co-cultures. These findings should lead to better understanding of the molecular basis of allergen-induced Th2 cell polarization and in doing so paves the way for the rational design of novel intervention strategies by targeting allergen receptors on innate immune cells or their carbohydrate counterstructures on allergens.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allergens / immunology
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Allergens / metabolism
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Animals
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Antigens, CD / metabolism*
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Antigens, Dermatophagoides / immunology
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Antigens, Dermatophagoides / metabolism*
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Arthropod Proteins / immunology
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Arthropod Proteins / metabolism*
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Biological Transport / drug effects
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Biological Transport / immunology
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Cell Adhesion Molecules / chemistry
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Cell Adhesion Molecules / metabolism*
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Cell Adhesion Molecules / pharmacology
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Coculture Techniques
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Cysteine Endopeptidases / immunology
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Cysteine Endopeptidases / metabolism*
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dogs
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Dose-Response Relationship, Drug
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Down-Regulation / drug effects
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Humans
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Lectins, C-Type / chemistry
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Lectins, C-Type / metabolism*
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Mice
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NIH 3T3 Cells
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Protein Binding
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Pyroglyphidae / immunology*
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / metabolism*
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Solubility
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Staining and Labeling
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Th2 Cells / cytology
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Th2 Cells / drug effects
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Allergens
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Antigens, CD
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Antigens, Dermatophagoides
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Arthropod Proteins
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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ICAM3 protein, human
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Lectins, C-Type
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Receptors, Cell Surface
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allergen Can f I
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Cysteine Endopeptidases
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Dermatophagoides pteronyssinus antigen p 1