Monocytes/Macrophages play a pathogenic role in IL-23 mediated psoriasis-like skin inflammation

Psoriasis is an immune-mediated inflammatory skin disease that affects millions worldwide. Studying immune cells involved in psoriasis pathogenesis is essential to identify effective and safe therapeutics for the disease. Using human psoriasis skin, activated macrophages were observed in both lesional and non-lesional skin, but were elevated in lesional skin. Activation of the IL-23/IL-17 pathway is integral to the development of psoriasis. To further characterize the monocyte/macrophage (Mon/Mac) population when the IL-23 pathway is activated, a murine model of intradermal injection of IL-23 was used. Flow cytometry revealed that Mon/Mac cells were the dominant immune population, particularly late in the model, highlighted by strong presence of Ly6C(hi)MHC II(hi) cells. The Mon/Mac cells were also shown to have high expression for TNFα but not IL-17A. Prophylactic dosing of a CSF-1R inhibitor to deplete Mon/Mac cells significantly reduced several inflammatory mediators from the skin tissue suggesting a pathogenic role for Mon/Mac. Treatment dosing of the inhibitor produced a less robust effect. Mon/Mac cells were also differentiated by levels of Ki67 and TNFα expression. These data point to an important contribution of Mon/Mac cells in IL-23 related skin inflammation and suggest that these cells are a significant player in the underlying pathophysiology of psoriasis.