title: Human dendritic cells express the IL-18R and are chemoattracted to IL-18.
abstract: IL-18 is secreted by a variety of cells such as epithelial cells, macrophages, and dendritic cells (DC), in particular, in areas of chronic inflammation. The effects of IL-18 are complex and not fully understood thus far. We sought to explore human DC as a new target for IL-18, since IL-18R expression has been described on myeloid cells such as macrophages and DC are likely to get in contact with IL-18 at sites of inflammatory reactions. We demonstrate the expression of the IL-18R on human DC in peripheral blood and epidermis, as well as monocyte-derived dendritic cells (MoDC). On MoDC, IL-18R expression is up-regulated by IFN-gamma. IL-18 strongly up-regulated CD54 on MoDC, whereas the effect on MHC class II, CD83, and CD86 was only moderate and the expression of CD40 and CD80 was not affected. MoDC primed with IL-18 did not increase their capacity to stimulate the proliferation or IFN-gamma production of autologous T cells. However, IL-18 had a direct migratory effect on MoDC as indicated by induction of filamentous actin polymerization and migration in Boyden chamber experiments. In epidermal DC, IL-18 was also able to induce filamentous actin polymerization. Therefore, IL-18 might represent a novel mechanism to recruit DC to areas of inflammation, in particular under Th1 cytokine conditions where IFN-gamma is increased such as psoriasis or inflammatory bowel diseases.
authors.affiliation: Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany. rgutzmer@gmx.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.forename: Katja
authors.initials: K
authors.lastname: Langer
authors.forename: Susanne
authors.initials: S
authors.lastname: Mommert
authors.forename: Miriam
authors.initials: M
authors.lastname: Wittmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Kapp
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D020382:Interleukin-18 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D053724:Receptors, Interleukin-18; D000097802:CD83 Antigen
chemical_list: D000199:Actins; D015703:Antigens, CD; D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D000097802:CD83 Antigen; C497964:CD86 protein, human; C508572:IL18R1 protein, human