title: The effect of Dermatophagoides pteronyssinus group 7 allergen (Der p 7) on dendritic cells and its role in T cell polarization.
abstract: The innate signaling pathway for Th2 immunity activated by inhaled allergens has not been well defined. Dendritic cells (DCs) can use their innate pattern-recognition Toll-like receptors and C-type lectin receptors to generate innate immunity and influence adaptive responses. The aim of this study was to investigate the glycoform of Dermatophagoides pteronyssinus group 7 allergen (Der p 7) and its functional interaction with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). Both bone marrow-derived dendritic cells (BMDCs) derived from mice and monocyte-derived DCs (MDDCs) derived from human peripheral blood mononuclear cells (PBMCs) were used to investigate the function of Der p 7. Dendritic cells derived from THP1 were used to investigate the glycol form of Der p 7. Der p 7 interacted with DC-SIGN as recognized by immunoprecipitation and glycoprotein staining, and its function was partially inhibited by deglycosylation. When BMDCs were cultured with Der p 7, the secretion of IL-6 and gene expressions of IL-6, OX40L and Jagged-1 were increased. IL4(+)/CD4(+) T cells could be induced by Der p 7, however IFN-γ(+)/CD4(+) T cells were down-regulated. The effects of Der p 7 on DCs were down-regulated in the presence of DC-SIGN or TLR4 antibodies and deglycosylation. rDer p 7 enhanced the DC differentiation of CD80 and CD86. The effects of Der p 7 pulsed-MDDCs on IL4(+)/CD4(+) and IFN-γ(+)/CD4(+) T-cell differentiation of human PBMCs were significantly increased after Der p 7 stimulation and decreased by DC-SIGN antibody inhibition. In conclusion, the Der p 7 is a glycoprotein and its function was partially through glycan binding. BMDCs could be activated by Der p 7 through TLR4 and DC-SIGN, and followed by the expression of OX40 ligand (OX40L) and Jagged-1, the expressions of IL4(+)/CD4(+) cells were enhanced. These findings identify a previously unrecognized function of Der p 7 and establish a link between innate TLR4/C-type lectin receptors and adaptive Th2 immunity.
authors.affiliation: Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Jaw-Ji
authors.initials: JJ
authors.lastname: Tsai
authors.affiliation: College of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Chiu
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei, Taiwan. Electronic address: enchih@mmc.edu.tw.
authors.forename: En-Chih
authors.initials: EC
authors.lastname: Liao
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins / Q000276:immunology*; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D006801:Humans; D000072100:Jagged-1 Protein / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D053262:Receptors, OX40 / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000072100:Jagged-1 Protein; D037181:Lectins, C-Type; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D053262:Receptors, OX40; D051197:Toll-Like Receptor 4; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C451244:Dermatophagoides pteronyssinus antigen p 7
keywords: C-type lectin receptor; DC-SIGN; Dendritic cell; Der p 7; Dermatophagoides pteronyssinus