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- Title
Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk.
- Authors
Tortola, Luigi; Rosenwald, Esther; Abel, Brian; Blumberg, Hal; Schäfer, Matthias; Coyle, Anthony J.; Renauld, Jean-Christoph; Werner, Sabine; Kisielow, Jan; Kopf, Manfred
- Abstract
Psoriasis is a chronic inflammatory disorder of the skin affecting approximately 2% of the world's population. Accumulating evidence has revealed that the IL-23/IL-17/IL-22 pathway is key for development of skin imrau-nopathology. However, the role of keratinocytes and their crosstalk with immune cells at the onset of disease remains poorly understood. Here, we show that IL-36R-deficient (Il36r-/-) mice were protected from imiqui-mod-induced expansion of dermal IL-17-producing γδ T cells and psoriasiform dermatitis. Furthermore, IL-36R antagonist-deficient (Il36rn-/-) mice showed exacerbated pathology. TLR7 ligation on DCs induced IL-36-mediated crosstalk with keratinocytes and dermal mesenchymal cells that was crucial for control of the pathological IL-23/IL-17/IL-22 axis and disease development. Notably, mice lacking IL-23, IL-17, or IL-22 were less well protected from disease compared with I136r-/- mice, indicating an additional distinct activity of IL-36 beyond induction of the pathological IL-23 axis. Moreover, while the absence of IL-1R1 prevented neu-trophil infiltration, it did not protect from acanthosis and hyperkeratosis, demonstrating that neutrophils are dispensable for disease manifestation. These results highlight a central and unique IL-l-independent role for IL-36 in control of the IL-23/IL-17/IL-22 pathway and development of psoriasiform dermatitis.
- Subjects
SKIN inflammation; KERATINOCYTES; PSORIASIS; MESENCHYMAL stem cells; KERATOSIS; INTERLEUKINS
- Publication
Journal of Clinical Investigation, 2012, Vol 122, Issue 11, p3965
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI63451