Induced psoriasis-like inflammation in an air pouch mouse model
Filippos T Charitidis1,*, Dina SM Damlund1, Naila Svitacheva1,  Janne Koch1  

1 LEO Pharma A/S, Department of In Vivo Biology & Safety, Ballerup, Denmark 

* filippos.charitidis@outlook.com 

Abstract 
Human psoriasis is a complex autoimmune skin disease, affecting a significant number of the global population. The initiation pathway comprises the differentiation and infiltration of Th17 cells into the skin and is characterized by the production of IL-17A and IL-17F cytokines. This results in a downstream cascade of events, including an exacerbated inflammatory response. In order to establish a more simplified mechanistic mouse model of psoriasis inflammation, we utilized the 6-day air pouch mouse model and aimed for the induction of a psoriasis-like inflammation by injecting a cocktail of inflammatory triggers into the air pouch cavity. The combination of anti-CD3 and IL-23 with or without IL-1β resulted in significantly increased IL-17A and IL-17F intra-pouch levels, and triggered a downstream production of the CXCL1 chemokine. The produced cytokines were detectable even 72 hours post-induction. In addition, TCRβ was downregulated on the cell surface of CD4 and CD8 positive T cells, indicating intra-pouch T cell activation. The presence of anti-CD3 seemed to be important for the increased production of the IL-17 cytokines, even at low concentrations. Furthermore, anti-CD3 induced CD3 positive cell migration into the subcutis and the lining tissue surrounding the air pouch cavity. In conclusion, the induced air pouch mouse model can mirror the IL-23/IL-17 axis of psoriasis-like inflammation.