Differential regulation of IDO activity in human dendritic cells through ligation of different c-type lectins: implications for allergic sensitization (P6055)

Abstract

Abstract Indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan metabolism, plays a critical role in regulating immune responses. IDO has been shown to have a protective effect in different models of experimental allergy and asthma however its role in human allergy has remained elusive. Recent work by our group showed that Der p 1 (a major house dust mite allergen), through engaging mannose receptor (MR) on dendritic cells (DCs), could modulate IDO activity. This in turn was shown to bias immune responses towards a Th2 phenotype. Here we studied the relationship between two major ‘allergen receptors’ on DCs namely MR and DC-SIGN in regulating IDO activity in order to further define the role of these receptors in controlling allergen induced Th2 immune responses. Our data indicates that IDO expression and activity in human DCs can be differentially regulated by engagement of MR and DC-SIGN. Intriguingly, we have shown that simultaneous activation of DCs with LPS (a known inducer of IDO activity) and either MR or DC-SIGN ligands has opposing effects on IDO activity in DCs with the MR ligation causing a decrease in IDO activity whilst DC-SIGN engagement causing an increase. Such opposing effect is likely due to differential activation of a number of downstream signalling molecules. Better understanding of these pathways could shed light on a range of host-pathogen interactions involving these key receptors including those occurring in the context of allergic sensitisation.