TRIM21 is important in the early phase of inflammation in the imiquimod-induced psoriasis-like skin inflammation mouse model

Tripartite motif-containing protein 21 ( TRIM21) regulates pro-inflammatory cytokines and type I interferons and acts as an autoantigen in certain autoimmune diseases, but TRIM21 has not been investigated in psoriasis. It has been suggested that TRIM21 may have a dual function; in the early phase of inflammation, it may function as a stimulator; but upon immune stimulation, its ubiquitinating mode of action may shift from stabilization to degradation of IRF3 causing inhibition of the immune responses. The imiquimod (IMQ)-induced psoriasis-like mouse model displays features similar to those of human psoriasis. However, chronicity is lacking in this model. We investigated whether the role of TRIM21 in psoriasis was pro-inflammatory or anti-inflammatory. We hypothesized that a shift of the TRIM21-ubiquitinating mode of action may explain the lack of chronicity in the IMQ-induced psoriasis-like mouse model. We showed that TRIM21 expression is increased in lesional psoriatic skin and in the early phase of IMQ-induced inflammation both in vitro and in vivo. Surprisingly, inflammation was significantly less pronounced in TRIM21 knockout mice than in wild-type mice as shown by ear thickness measured at days 8, 9 and 10 after treatment start, by spleen weight as a marker of systemic effect of IMQ at 10 days after treatment start and by expression of IL-12p40 at days 3 and 10 after treatment start and IL-17A at day 3 after treatment start. Therefore, induction of TRIM21 expression cannot explain the lack of chronicity in the IMQ-induced psoriasis-like skin inflammation mouse model.