Trim32 Deficiency Enhances Th2 Immunity and Predisposes to Features of Atopic Dermatitis

Altered innate immunity is a feature of certain skin inflammatory diseases such as psoriasis and atopic dermatitis (AD). In this study, we provide evidence that deficiency in Trim32 (a tripartite motif [TRIM] protein with innate antiviral activity) contributes to a T helper type 2 biased response and predisposes to features of AD in mice. On treatment with the toll-like receptor 7 agonist imquimod (IMQ), Trim32 knockout mice displayed compromised psoriasiform phenotypes and defective T helper type 17 response. Instead, IMQ treatment of Trim32 knockout mice induced AD-like phenotypes with enhanced skin infiltration of eosinophils and mast cells, elevation of T helper type 2 cytokines/chemokines expression, and reduced expression of filaggrin protein expression. Furthermore, although the induction of phosphorylated Stat3 and RelA was compromised after IMQ treatment in the knockout mice, phosphorylated Stat6 was elevated. CC chemokine ligand 20 induction by tumor necrosis factor-α and IL-17A was reduced in Trim32-deficient keratinocytes, whereas CC chemokine ligand 5 induction by tumor necrosis factor-α and IL-4 was enhanced. In addition, Trim32 protein levels were elevated in mice treated with IMQ. Unlike Trim32 overexpression in psoriasis, TRIM32 levels were low in patients with AD. Based on Trim32 induction by IMQ, the lower levels of TRIM32 in AD skin compared with healthy control and psoriatic skin suggest a defective TRIM32 pathway in AD pathogenesis.