Macrophages play a pathogenic role in IL-23 mediated psoriasiform skin inflammation

Abstract

Abstract Psoriasis (Ps) is an immune-mediated inflammatory skin disease that affects millions worldwide. Studying immune cells involved in Ps pathogenesis is essential to identify effective and safe therapeutics for the disease. Recent studies have demonstrated the involvement of macrophages in human Ps skin. Using an IL-23 murine model of psoriasiform dermatitis, which closely models human Ps, we have characterized the cellular lineage during disease progression and found continuous infiltration of macrophage as dominant immune population. Depletion of macrophages in the IL-23 murine model significantly reduced the inflammation as well as inflammatory mediators, such as TNFa, in the skin. This strongly suggests a pathogenic role of macrophages in the psoriasiform skin inflammation. Further characterization of this model revealed a number of phenotypically distinct macrophage populations suggesting they may play different roles in disease progression. Collectively, our data suggests that targeting macrophages may have therapeutic benefit for Ps patients.