[HTML][HTML] IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis

E Witte, G Kokolakis, K Witte, S Philipp… - Journal of Investigative …, 2014 - Elsevier
E Witte, G Kokolakis, K Witte, S Philipp, WD Doecke, N Babel, BM Wittig, K Warszawska…
Journal of Investigative Dermatology, 2014Elsevier
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 …
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.
Elsevier