title: Human beta-defensin 3 induces maturation of human langerhans cell-like dendritic cells: an antimicrobial peptide that functions as an endogenous adjuvant.
abstract: Human beta-defensins (hBDs) are antimicrobial peptides that have an important role in innate immune responses at epithelial barriers such as the skin. However, the role that hBDs have in initiating cellular immune responses that contribute to antigen-specific adaptive immunity is not well understood. Here we show that one member of the hBD family, hBD3, can induce maturation and T-helper type 1 skewing function in human Langerhans cell-like dendritic cells (LC-DCs). Specifically, hBD3 potently induces phenotypic maturation of LC-DCs, including increased expression of CCR7, which mediates functional chemotactic responses to CCL19 and CCL21. hBD3-stimulated LC-DCs induce strong proliferation of and IFN-γ secretion by naive human T cells. hBD3 also induces phenotypic maturation of primary human skin-migratory DCs derived from human skin explants. These results suggest an important role for hBD3 in inducing DC activation, migration, and polarization. Thus, hBD3 contributes to the integration of innate and adaptive immune responses in the skin, and may be a useful adjuvant for skin immunization and an important factor in the pathophysiology of inflammatory skin diseases.
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. ferrislk@upmc.edu
authors.forename: Laura K
authors.initials: LK
authors.lastname: Ferris
authors.forename: Yvonne K
authors.initials: YK
authors.lastname: Mburu
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Mathers
authors.forename: Eric R
authors.initials: ER
authors.lastname: Fluharty
authors.forename: Adriana T
authors.initials: AT
authors.lastname: Larregina
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.forename: Louis D
authors.initials: LD
authors.lastname: Falo
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D054415:Chemokine CCL19 / Q000276:immunology / Q000378:metabolism; D054421:Chemokine CCL21 / Q000276:immunology / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization / Q000379:methods*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D023083:beta-Defensins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D023181:Antimicrobial Cationic Peptides; C515460:CCL19 protein, human; C515478:CCL21 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; C422950:DEFB103A protein, human; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D023083:beta-Defensins; D007371:Interferon-gamma; D019206:GTP-Binding Protein alpha Subunits, Gi-Go