Loss of extracellular superoxide dismutase induces severe IL-23-mediated skin inflammation in mice.

Psoriasis is a common chronic and complex autoimmune inflammatory skin disorder. The histological characteristics of psoriasis are epidermal hyperplasia, mononuclear leukocyte infiltration into the dermis, and increased angiogenesis. However, the mechanisms involved in the pathogenesis of psoriasis remain unclear. Extracellular superoxide dismutase (EC-SOD) has antichemotactic activities. Because immune cell infiltration is seen in psoriatic lesions and psoriasis patients express low levels of EC-SOD, we hypothesized that the lack of EC-SOD induces more severe IL-23-mediated psoriasis-like skin inflammation. To test this hypothesis, we determined whether the loss of EC-SOD causes more severe IL-23-induced skin inflammation. Ear skin after IL-23 administration was thicker in EC-SOD knockout (KO) mice compared with wild-type mice. In addition, infiltration of CD4(+) T cells, macrophages, and dendritic cells (DCs) into IL-23 injection sites was more elevated in EC-SOD KO mice. The expression of proinflammatory cytokines and chemokines was also more elevated in EC-SOD KO mice, and EC-SOD KO DCs expressed a higher level of MHCII. Finally, EC-SOD transgenic mice showed much less severe IL-23-induced skin inflammation. Therefore, EC-SOD may inhibit IL-23-induced psoriasis-like inflammation through the inhibition of immune cell infiltration and immune responses. These results suggest that EC-SOD could be a possible candidate for management of psoriasis.