Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes

Kerstin Wolk^*^,1, Katrin Witte^*, Ellen Witte^*, Susanna Proesch, Gundula Schulze-Tanzil, Katarzyna Nasilowska^*, John Thilo, Khusru Asadullah^||, Wolfram Sterry^¶, Hans-Dieter Volk^# and Robert Sabat^*

^* Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany;
Institute of Virology, University Hospital Charité, Berlin, Germany;
Institute of Anatomy, University Hospital Charité, Berlin, Germany;
Department of Trauma and Reconstructive Surgery, University Hospital Charité, Berlin, Germany;
^|| Global Drug Discovery; Bayer Schering Pharma, Berlin, Germany;
^¶ Department of Dermatology, University Hospital Charité, Berlin, Germany; and
^# Institute of Medical Immunology, University Hospital Charité, Berlin, Germany

¹Correspondence: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Campus-Charité Mitte, University Hospital Charité, Charitéplatz 1, D-10117 Berlin, Germany. E-mail: kerstin.wolk{at}charite.de

IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29 are newmembers of the IL-10 interferon family. Monocytes are well-knownsources of IL-19, IL-20, and IL-24. We demonstrated here thatmonocytes also expressed IL-29, and monocyte differentiationinto macrophages (M ${phi}$ ) or dendritic cells (DCs) strongly changedtheir production capacity of these cytokines. Maturation ofDCs with bacterial stimuli induced high expression of IL-28/IL-29and IL-20. Simulated T cell interaction and inflammatory cytokinesinduced IL-29 and IL-20 in maturing DCs, respectively. Comparedwith monocytes, DCs expressed only minimal IL-19 levels andno IL-24. The differentiation of monocytes into M ${phi}$ reduced theirIL-19 and terminated their IL-20, IL-24, and IL-29 productioncapacity. Like monocytes, neither M ${phi}$ nor DCs expressed IL-22or IL-26. The importance of maturing DCs as a source of IL-28/IL-29was supported by the much higher mRNA levels of these mediatorsin maturing DCs compared with those in CMV-infected fibroblasts,and the presence of IL-28 in lymph nodes but not in liver oflipopolysaccharide-injected mice. IL-19, IL-20, IL-22, IL-24,and IL-26 do not seem to affect M ${phi}$ or DCs as deduced from thelack of corresponding receptor chains. The significance of IL-20and IL-28/IL-29 coexpression in maturing DCs may lie in thebroadly amplified innate immunity in neighboring tissue cellslike keratinocytes. In fact, IL-20 induced the expression ofantimicrobial proteins, whereas IL-28/IL-29 enhanced the expressionof toll-like receptors (TLRs) and the response to TLR ligands.However, the strongest response to TLR2 and TLR3 activationshowed keratinocytes in the simultaneous presence of IL-20 andIL-29.

Key Words: interferon-lambda • cytomegalovirus • chondrocytes • TLR2 • TLR3 • legumain