Role of host lipid metabolism and tissue macrophages in psoriasis

Epidemiologic studies and clinical co-morbidity suggests a link between psoriasis and atherosclerosis. These conditions share common inflammatory mediators, including macrophage (Mp) signaling and the presence of oxidized low-density lipoprotein (LDL). We examined the role of lipid metabolism and tissue Mp in psoriasis. Using immunohistochemistry on psoriatic tissue, we identified a subpopulation of CD209+/CD163+ dermal Mp which have phagocytic properties and are capable of engulfing oxidized lipids. Next, using gene-expression arrays, we examined the effect of oxidized lipids on Mp signaling. Treatment of THP-1 Mp with a component of minimally oxidized LDL induced the expression of interleukins-1, -6, -15, -17, -23, cathelicidin and vascular endothelial growth factor, all of which play a role is psoriasis. Lastly, we examined the properties of high-density lipoprotein (HDL) in serum from psoriatic patients. In healthy patients, HDL is capable of reverse cholesterol transport and has potent anti-inflammatory properties. In patients with systemic inflammatory disease, including atherosclerosis, HDL loses these properties and becomes dysfunctional. Using a well-established model of monocyte chemotaxis as well as an in-vitro model of IL-23 production, both as markers of inflammation, we demonstrated that HDL from psoriatic patients was dysfunctional and had pro-inflammatory properties. Taken together, these data provide a role for tissue Mp and host lipid metabolism in psoriasis