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

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 (M phi) 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 M phi reduced their IL-19 and terminated their IL-20, IL-24, and IL-29 production capacity. Like monocytes, neither M phi 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 M phi or DCs as deduced from the lack of corresponding receptor chains. The significance of IL-20 and IL-28/IL-29coexpression 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.