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 Th2 biased response and predisposes to features of AD in mice. Upon treatment with the TLR7 agonist imquimod (IMQ), Trim32 knockout (KO) mice displayed compromised psoriasiform phenotypes and defective Th17 response. Instead, IMQ treatment of Trim32 KO mice induced AD-like phenotypes with enhanced skin infiltration of eosinophils and mast cells, elevation of Th2 cytokines/chemokines expression, and reduced expression of filaggrin protein expression. Furthermore, while the induction of phosphorylated Stat3 and RelA were compromised following IMQ treatment in the KO mice, phosphorylated Stat6 was elevated. CCL20 induction by TNFα and IL-17A was reduced in Trim32 deficient keratinocytes whereas CCL5 induction by TNFα 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 AD patients. Based on Trim32 induction by IMQ, the lower levels of TRIM32 in AD skin compared to healthy control and psoriatic skin suggest a defective TRIM32 pathway in AD pathogenesis.