Abstract
Dendritic cells (DC) are instrumental in orchestrating an appropriately polarized Th cell response to pathogens. DC exhibit considerable phenotypic and functional plasticity, influenced by lineage, Ag engagement, and the environment in which they develop and mature. In this study, we identify the human cationic peptide LL-37, found in abundance at sites of inflammation, as a potent modifier of DC differentiation, bridging innate and adaptive immune responses. LL-37-derived DC displayed significantly up-regulated endocytic capacity, modified phagocytic receptor expression and function, up-regulated costimulatory molecule expression, enhanced secretion of Th-1 inducing cytokines, and promoted Th1 responses in vitro. LL-37 may be an attractive therapeutic candidate for manipulating T cell polarization by DC.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Adjuvants, Immunologic / pharmacology*
- Amino Acid Sequence
- Animals
- Antigens / metabolism
- Antimicrobial Cationic Peptides / pharmacology*
- Cathelicidins
- Cattle
- Cell Differentiation / immunology
- Cell Division / immunology
- Cells, Cultured
- Chemotaxis / immunology
- Cytokines / biosynthesis
- Dendritic Cells / cytology*
- Dendritic Cells / immunology*
- Dendritic Cells / metabolism
- Dendritic Cells / ultrastructure
- Endocytosis / immunology
- GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
- Humans
- Interferon-gamma / metabolism
- Molecular Sequence Data
- Receptors, G-Protein-Coupled / physiology
- Receptors, Immunologic / biosynthesis
- T-Lymphocyte Subsets / cytology
- T-Lymphocyte Subsets / immunology*
- T-Lymphocyte Subsets / metabolism*
- Th1 Cells / immunology
- Th1 Cells / metabolism
Substances
- Adjuvants, Immunologic
- Antigens
- Antimicrobial Cationic Peptides
- Cathelicidins
- Cytokines
- Receptors, G-Protein-Coupled
- Receptors, Immunologic
- Interferon-gamma
- GTP-Binding Protein alpha Subunits, Gi-Go