title: Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression.
abstract: In vivo evidence suggests that interleukin-18 (IL-18) shapes the development of adaptive immunity toward T-helper cell type 1 (Th1) responses. Monocyte-derived dendritic cells 1 (DC1s) preferentially induce a Th1 response, while plasmacytoid DC-derived DC2s have been linked to a Th2 response. We analyzed the role of IL-18 during the initiation phase of a Th response in vitro to elucidate the basis of these in vivo observations. IL-18 was constitutively released from DC1s, but not DC2s. Neutralization of IL-18 in coculture experiments of DC1s with allogeneic naive T lymphocytes did not alter the Th1/Th2 phenotype, while anti-IL-12 efficiently down-regulated the Th1 response. Unexpectedly, IL-18 receptor (IL-18R) alpha and beta chains were expressed on DC2 lineage. IL-18R expression was functional, as IL-18 induced chemotaxis in plasmacytoid DCs (pre-DC2s) and enhanced the allostimulatory capacity of IL-3-differentiated DC2s. Pre-DC2s exposed to IL-18 skewed the development of Th cells toward Th1 in coculture experiments of DC2s and allogeneic naive T cells, which was inhibited by IL-12 p70 neutralization. IL-18 might have a profound role during the initiation phase of an immune response by recruiting pre-DC2s and modulating the function of DC2s.
mesh_terms: D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000097:blood; D017931:DNA Primers; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020382:Interleukin-18 / Q000494:pharmacology* / Q000502:physiology; D053727:Interleukin-18 Receptor alpha Subunit; D007377:Interleukin-3 / Q000494:pharmacology; D008213:Lymphocyte Activation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics*; D053724:Receptors, Interleukin-18; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D017931:DNA Primers; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D007377:Interleukin-3; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18