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

Authors
  • Bech, Rikke1, 2
  • Jalilian, Babak2
  • Agger, Ralf3
  • Iversen, Lars1
  • Erlandsen, Mogens4
  • Otkjaer, Kristian1
  • Johansen, Claus1
  • Paludan, Søren R.2
  • Rosenberg, Carina A.2
  • Kragballe, Knud1
  • Vorup-Jensen, Thomas2, 5, 6
  • 1 Aarhus University Hospital, Department of Dermatology, Aarhus, Denmark , Aarhus (Denmark)
  • 2 Aarhus University, Department of Biomedicine, Aarhus, Denmark , Aarhus (Denmark)
  • 3 Aalborg University, Department of Health Science and Technology, Aalborg, Denmark , Aalborg (Denmark)
  • 4 Aarhus University, Department of Public Health - Biostatistics, Aarhus, Denmark , Aarhus (Denmark)
  • 5 Aarhus University, Interdisiplinary Nanoscience Center, Aarhus, Denmark , Aarhus (Denmark)
  • 6 Aarhus University, Biophysical Immunology Laboratory, Department of Biomedicine, The Bartholin Building (1240), Wilhelm Meyers Allé 4, Aarhus C, DK-8000, Denmark , Aarhus C (Denmark)
Type
Published Article
Journal
Molecular and Cellular Therapies
Publisher
"ClinTransMed, AB"
Publication Date
Jan 26, 2016
Volume
4
Issue
1
Identifiers
DOI: 10.1186/s40591-016-0046-x
Source
Springer Nature
Keywords
License
Green

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.

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