Establishment Of An Intradermal Ear Injection Model Of Il-17a And Il-36 Gamma As A Tool To Investigate The Psoriatic Cytokine Network

Psoriasis is a chronic skin disease affecting 2-3% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36 gamma plays also a pathogenic role. To understand more precisely the role of the IL-17A-IL-36 gamma cytokine network in skin pathology, we used an ear injection model. We injected IL-17A or IL-36 gamma alone and in combination into the ear pinnae of mice. This resulted in a significant increase in ear thickness measured over time. Histological evaluation of IL-17A + IL-36 gamma-treated skin showed a strong acanthosis, hyperparakeratosis and infiltration of neutrophils. The same histological features were found in mice after injection of IL-36 gamma alone, but to a lesser extent. IL-17A alone was not able to induce psoriasis-like changes. Genes encoding proteins of the S100 family, antimicrobial peptides and chemo-attractants for neutrophils were upregulated in the IL-17A + IL-36 gamma group. A much weaker expression was seen after the injection of each cytokine alone. These results strengthen the hypothesis that IL-17A and IL-36 gamma drive psoriatic inflammation via a synergistic interaction. Our established intradermal ear injection model can be utilized in the future to monitor effects of various inhibitors of this cytokine network.