The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization.
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.
Davidson
Donald J
DJ
British Columbia Research Institute for Child and Family Health, Room 381, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5Z 4H4. ddavidso@interchange.ubc.ca
Currie
Andrew J
AJ
Reid
Gregor S D
GS
Bowdish
Dawn M E
DM
MacDonald
Kelly L
KL
Ma
Rebecca C
RC
Hancock
Robert E W
RE
Speert
David P
DP
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D054804:Cathelicidins; D002417:Cattle; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000276:immunology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000941:Antigens; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D019206:GTP-Binding Protein alpha Subunits, Gi-Go