Exaggerated IDO1 expression and activity in Langerhans cells from patients with atopic dermatitis upon viral stimulation: a potential predictive biomarker for high risk of Eczema herpeticum.

Abstract

Atopic dermatitis (AD) is a heterogenous and highly complex disease characterized by an increased microbial colonization. For unknown reasons, a subgroup of patients with AD develops Eczema herpeticum (EH), a severe viral complication due to spreading of herpes simplex virus (HSV). Indoleamine 2,3-dioxygenase (IDO1) is a tryptophan (Trp)-catabolizing enzyme which is assumed to be instrumental in the antibacterial and antiviral defence mechanisms. Comparative investigation of the IDO1 expression and activity in freshly isolated monocytes, plasmacytoid DC (pDC) and in vitro-generated Langerhans cells (LC) obtained from AD patients with HSV infections and EH and nonatopic controls. We demonstrate an increase in Trp degradation in the serum of patients during acute EH episodes. Circulating pDC from patients with history of EH display an increased IDO1 expression. An increased Trp degradation is detected in the supernatants of circulating monocytes from AD patients with acute EH. Mature LC from AD patients with history of EH and with acute EH display an increased IDO1 expression and activity, respectively. In LC from patients with history of EH, viral signals induce an exaggerated IDO1 expression and activity. IDO1 expression and activity in LC seem to be involved in the pathophysiology of EH in AD and could represent a predictive biomarker for patients with risk to develop EH and other viral complications.