Complement component 3 prevents imiquimod-induced psoriatic skin inflammation by inhibiting apoptosis in mice

Abstract

Complement component 3 (C3), a pivotal molecule in the complement system, is an essential immune mediator in various diseases, including psoriasis. However, the mechanistic role of C3 in psoriasis pathology and development remains elusive. Here, we showed that C3 deficiency dramatically augmented imiquimod-induced psoriasis-like skin inflammation, characterized by greater epidermal hyperplasia, inflammatory cell infiltration, and inflammatory gene expression than those in wild-type counterparts. In addition, C3 deficiency promoted imiquimod-induced skin cell apoptosis and supported greater proportions of IFN-γ⁺ T cells in the inflamed tissues. Accordingly, C3 supplement in the C3 deficient mice reduced skin inflammation and cells apoptosis. Moreover, blocking apoptosis with Z-VAD-FMK, a broad caspase inhibitor, markedly attenuated imiquimod-induced psoriasis-like skin inflammation and IFN-γ⁺ T cell responses in C3-deficient mice. Collectively, our results suggest that C3 prevents imiquimod-induced psoriasis-like skin inflammation by inhibiting apoptosis.

Keywords: Apoptosis; Complement component 3; IFN-γ; Psoriasis; T cell.