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 play an important role in innate immune responses at epithelial barriers such as the skin. However, the role that hBDs play 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 (Th1) skewing function in human Langerhans cell-like DCs (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 and IFN-γ secretion by naïve human T cells. HBD3 also induces phenotypic maturation of primary human skin-migratory dendritic cells 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.