Human dendritic cells express the IL-18R and are chemoattracted to IL-18.
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.
Gutzmer
Ralf
R
Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany. rgutzmer@gmx.de
Langer
Katja
K
Mommert
Susanne
S
Wittmann
Miriam
M
Kapp
Alexander
A
Werfel
Thomas
T
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
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