title: Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes.
abstract: IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29 are new members of the IL-10 interferon family. Monocytes are well-known sources of IL-19, IL-20, and IL-24. We demonstrated here that monocytes also expressed IL-29, and monocyte differentiation into macrophages (Mphi) or dendritic cells (DCs) strongly changed their production capacity of these cytokines. Maturation of DCs with bacterial stimuli induced high expression of IL-28/IL-29 and IL-20. Simulated T cell interaction and inflammatory cytokines induced IL-29 and IL-20 in maturing DCs, respectively. Compared with monocytes, DCs expressed only minimal IL-19 levels and no IL-24. The differentiation of monocytes into Mphi reduced their IL-19 and terminated their IL-20, IL-24, and IL-29 production capacity. Like monocytes, neither Mphi nor DCs expressed IL-22 or IL-26. The importance of maturing DCs as a source of IL-28/IL-29 was supported by the much higher mRNA levels of these mediators in maturing DCs compared with those in CMV-infected fibroblasts, and the presence of IL-28 in lymph nodes but not in liver of lipopolysaccharide-injected mice. IL-19, IL-20, IL-22, IL-24, and IL-26 do not seem to affect Mphi or DCs as deduced from the lack of corresponding receptor chains. The significance of IL-20 and IL-28/IL-29 coexpression in maturing DCs may lie in the broadly amplified innate immunity in neighboring tissue cells like keratinocytes. In fact, IL-20 induced the expression of antimicrobial proteins, whereas IL-28/IL-29 enhanced the expression of toll-like receptors (TLRs) and the response to TLR ligands. However, the strongest response to TLR2 and TLR3 activation showed keratinocytes in the simultaneous presence of IL-20 and IL-29.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany. kerstin.wolk@charite.de
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.forename: Susanna
authors.initials: S
authors.lastname: Proesch
authors.forename: Gundula
authors.initials: G
authors.lastname: Schulze-Tanzil
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nasilowska
authors.forename: John
authors.initials: J
authors.lastname: Thilo
authors.forename: Khusru
authors.initials: K
authors.lastname: Asadullah
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons; D007378:Interleukins / Q000502:physiology*; D015603:Keratinocytes / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C422042:interleukin 20