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.

The role of transposable elements in the regulation of IFN-λ1 gene expression

“…Here, we show that in addition to MDDCs, IFN-1 expression is significantly induced in the human M-CSF-and GM-CSFderived macrophages (MPHs) (10 5 -and 10 4 -fold, respectively) (17) (Fig. S1 A), contrary to a previous study (16). The mRNA expression peaked at Ϸ2 h after LPS induction ( Fig.…”

“…Previous studies demonstrated that LPS-induced differentiation of MDDCs result in the rapid and robust expression of the IFN-1 gene (16). Here, we show that in addition to MDDCs, IFN-1 expression is significantly induced in the human M-CSF-and GM-CSFderived macrophages (MPHs) (10 5 -and 10 4 -fold, respectively) (17) (Fig.…”

Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines

“…Expression of the IL-20R1/IL-20R2 and IL-22R1/IL-20R2 heterodimers, which are required for IL-20 bioactivity, have been observed only on cells of epithelial origin including skin, lung, and testis (1,18,19). These data suggest a major role for IL-20 SFCs in mediating cross-talk between infiltrating immune cells (T cells, macrophages, and dendritic cells) that express the IL20SFCs, and the skin.…”

Structure and function of interleukin-22 and other members of the interleukin-10 family

“…In contrast to IL-22, which is mainly produced by TH17, NK, and NK-like cells, IL-20 is mainly a monocyte and dendritic cell product, like IL-19 [9,69]. Bacterial LPS also induces IL-20 expression in glial cells in the brain [70].…”