title: Mite allergen decreases DC-SIGN expression and modulates human dendritic cell differentiation and function in allergic asthma.
abstract: House dust mites (HDMs) induce allergic asthma in sensitized individuals, although how HDMs activate immature mucosal dendritic cells (DCs) to render the T helper cell type 2 (Th2)-mediated immune response is unclear. In this study, our results showed a significant calcium-dependent lectin binding of Dermatophagoides pteronyssinus (Der p) extracts to DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), the C-type lectin receptors (CLRs) of DCs. Moreover, monocyte-derived DCs (MDDCs) of Der p-sensitized asthmatics (AS) exhibited decreased expression of DC-SIGN, increased endocytosis, and impaired differentiation of DC precursors. The Der p-induced downregulation of DC-SIGN expression in the differentiation of immature MDDCs may be because of the internalization of Der p-DC-SIGN complex. MDDCs of AS produced more interleukin (IL)-6 and less IL-12p70 cytokines when stimulated with lipopolysaccharide (LPS) or Der p than those of nonallergic controls (NC). In the co-culture experiments, MDDCs pretreated with Der p induced GATA-3 expression and IL-4 cytokine productions in naive CD4(+) T cells. These effects of Der p on the differentiation and function of MDDCs could be partially blocked by anti-DC-SIGN antibodies. In conclusion, our results suggest a critical step of allergen sensitization that involves CLRs in the innate immune response of DCs, which may provide a therapeutic or preventive potential for allergic asthma.
authors.affiliation: Institute of Microbiology and Immunology, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Huang
authors.forename: Y-L
authors.initials: YL
authors.lastname: Lin
authors.forename: C-F
authors.initials: CF
authors.lastname: Liu
authors.forename: H-F
authors.initials: HF
authors.lastname: Kao
authors.forename: J-Y
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008925:Mites / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000485:Allergens; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin