title: TRIM21 is important in the early phase of inflammation in the imiquimod-induced psoriasis-like skin inflammation mouse model.
abstract: 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.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vinter
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Ane
authors.initials: A
authors.lastname: Langkilde
authors.affiliation: Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Vijole
authors.initials: V
authors.lastname: Ottosson
authors.affiliation: Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Espinosa
authors.affiliation: Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Wahren-Herlenius
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Raaby
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D006801:Humans; D000077271:Imiquimod; D018345:Mice, Knockout; D011565:Psoriasis / Q000139:chemically induced* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D000099207:SS-A Antigen
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D000077271:Imiquimod; D012261:Ribonucleoproteins; D000099207:SS-A Antigen
keywords: IL-17; IL-23; autoimmune; interferon; mouse-model