Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules

Abstract

BackgroundPsoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs.MethodsHere, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed IL-20 effects on DC maturation, receptor expression and signaling. By use of extra cellular matrix components mimicking the skin environment, we also studied the functional effects of IL-20 on the chemotactic migration of DCs. Based on the recent finding that CD18 integrin are shed during migration of myeloid leukocytes, the concentration of these adhesion molecules was measured in MDDCs culture supernatants post migration.ResultsFollowing stimulation with IL-20, immature human MDDCs enhanced the expression of the co-stimulatory molecule CD86, further enabling activation of the p38 MAPK, but not the STAT3, pathway. IL-20 increased the migration of MDDCs in a biphasic response narrowly controlled by the interleukin concentration. A concomitant change in the shedding of CD18 integrins suggested that these adhesion molecules play a role in the migration of the MDDCs through the extracellular matrix layer.ConclusionTaken together, our findings points to a possible, yet subtle, role of IL-20 in DCs migration. The biphasic response suggests that the aberrant IL-20 expression in psoriasis impedes DC migration, which could be a part of the processes that precipitates the dysregulated inflammatory response associated with this disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s40591-016-0046-x) contains supplementary material, which is available to authorized users.

IL-20 Signaling in Activated Human Neutrophils Inhibits Neutrophil Migration and Function

“…Involvement of p38 MAPK and ERK1/2 has also been reported in dendritic cells and endothelial cells, respectively (30, 33). Furthermore, IL-20 has been shown to activate ERK1/2 in rheumatoid arthritis synovial fibroblasts (24).…”

“…IL-20 has been reported to activate STAT3, p38 MAPK, or ERK 1/2 in different cell types (20, 22, 24, 30, 33). After exposure of neutrophils to IL-20, we found STAT3 phosphorylation to be minimal and inconsistent (not shown).…”

IL-20 receptor cytokines in autoimmune diseases

“…Similarly to IL-19, IL-20 suppresses the production of IL-17A from γδ T cells [24]. However, IL-20 is unique in being able to induce DCs maturation [38]. IL-20 also increases the expression of CD86 on human monocyte-derived DCs [38], pointing to a possible role during antigen presentation in regulating T cell activation in a indirect manner.…”

“…However, IL-20 is unique in being able to induce DCs maturation [38]. IL-20 also increases the expression of CD86 on human monocyte-derived DCs [38], pointing to a possible role during antigen presentation in regulating T cell activation in a indirect manner. Finally, IL-20 may affect DCs migration, due to its effects on the shedding of the integrin CD18 [38], This could potentially influence the ability of DC to migrate to lymphoid organs and secondarily affect their effectiveness as antigen presenting cells for elicitation of the adaptive immune response.…”

IL-26: An Emerging Proinflammatory Member of the IL-10 Cytokine Family with Multifaceted Actions in Antiviral, Antimicrobial, and Autoimmune Responses

“…Although the distribution of IL-10R2 is broad, only a subset of cells, particularly epithelial cells and keratinocytes, expresses IL-20R1 [ 11 ]. A recent report shows that myeloid cells, like monocyte-derived dendritic cells, also express mRNA for IL-20R1 [ 12 ]. This restricted expression pattern of IL-20R1 limits the action of IL-26.…”