title: IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis.
abstract: Psoriasis is a common chronic inflammatory disease with characteristic skin alterations and functions as a model of immune-mediated disorders. Cytokines have a key role in psoriasis pathogenesis. Here, we demonstrated that out of 30 individually quantified cytokines, IL-19 showed the strongest differential expression between psoriatic lesions and healthy skin. Cutaneous IL-19 overproduction was reflected by elevated IL-19 blood levels that correlated with psoriasis severity. Accordingly, anti-psoriatic therapies substantially reduced both cutaneous and systemic IL-19 levels. IL-19 production was induced in keratinocytes by IL-17A and was further amplified by tumor necrosis factor-α and IL-22. Among skin cells, keratinocytes were found to be important targets of IL-19. IL-19 alone, however, regulated only a few keratinocyte functions. While increasing the production of S100A7/8/9 and, to a moderate extent, also IL-1β, IL-20, chemokine C-X-C motif ligand 8, and matrix metalloproteinase 1, IL-19 had no clear influence on the differentiation, proliferation, or migration of these cells. Importantly, IL-19 amplified many IL-17A effects on keratinocytes, including the induction of β-defensins, IL-19, IL-23p19, and T helper type 17-cell- and neutrophil-attracting chemokines. In summary, IL-19 as a component of the IL-23/IL-17 axis strengthens the IL-17A action and might be a biomarker for the activity of this axis in chronic inflammatory disorders.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kokolakis
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Philipp
authors.affiliation: Global Biomarker, Bayer Pharma AG, Berlin, Germany.
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Doecke
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany; Department of Nephrology, University Hospital Charité, Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Babel
authors.affiliation: Medical Clinic 1 (Gastroenterology, Rheumatology, Infectiology), University Hospital Charité, Berlin, Germany.
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Wittig
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Warszawska
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Agata
authors.initials: A
authors.lastname: Kurek
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Erdmann-Keding
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kunz
authors.affiliation: Global Biomarker, Bayer Pharma AG, Berlin, Germany.
authors.forename: Khusru
authors.initials: K
authors.lastname: Asadullah
authors.affiliation: Department of Dermatology, Boston University, Roger Williams Medical Center, Providence, Rhode Island, USA.
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany; Institute of Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany; Research Center Immunosciences, University Hospital Charité, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany; Research Center Immunosciences, University Hospital Charité, Berlin, Germany. Electronic address: robert.sabat@charite.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; C421250:IL19 protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha