title: IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not.
abstract: Psoriasis is a common chronic skin disease with a largely unknown pathogenesis. We demonstrate here that transgenic over-expression of interleukin (IL)-22 in mice resulted in neonatal mortality and psoriasis-like skin alterations including acanthosis and hypogranularity. This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes. The comparison of cytokines with hypothesized roles in psoriasis pathogenesis determined that neither interferon (IFN)-gamma nor IL-17, but only IL-22 and, with lower potency, IL-20 caused psoriasis-like morphological changes in a three-dimensional human epidermis model. These changes were associated with inhibited keratinocyte terminal differentiation and with STAT3 upregulation. The IL-22 effect on differentiation-regulating genes was STAT3-dependent. In contrast to IL-22 and IL-20, IFN-gamma and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-alpha potently induced diverse chemokines and additionally enhanced the expression of IL-22 receptor pathway elements and amplified some IL-22 effects. This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Harald S
authors.initials: HS
authors.lastname: Haugen
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xu
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.forename: Kim
authors.initials: K
authors.lastname: Waggie
authors.forename: Monica
authors.initials: M
authors.lastname: Anderson
authors.forename: Elmar
authors.initials: E
authors.lastname: Vom Baur
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Warszawska
authors.forename: Sandra
authors.initials: S
authors.lastname: Philipp
authors.forename: Caroline
authors.initials: C
authors.lastname: Johnson-Leger
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat