Indoleamine 2,3-Dioxygenase is not required for tolerance induction in the airways but is important for allergic airway disease (39.8)

Abstract

Abstract Indoleamine 2,3 dioxgenase (IDO) has emerged as an important negative regulator of immune responses. However, the role of IDO in Th2 cell-mediated diseases is not completely clear. We investigated the role of IDO in the induction of inflammation or tolerance in the airways in response to ovalbumin (OVA). The results of these experiments show that IDO−/− mice are susceptible to tolerance induction. However, IDO−/− mice displayed significantly lower airway hyperresponsiveness (AHR), lower serum OVA-specific IgE and lower Th2 type cytokines (IL-5 and IL-13) in comparison to wt mice. In an OVA-induced chronic airway inflammation model, the IDO−/− mice also showed lower AHR and Th2 type cytokines in the lung and less infiltration of inflammatory cells in the airways. To dissect the mechanism underlying IDO-mediated promotion of allergic airway disease, we stimulated lung DC by allergens in vitro. The expression of important co-stimulatory molecules and MHC-II was lower in DCs from IDO−/− mice in comparison to those in DCs from wt control mice suggesting that the reduced airway Th2 type immune response in IDO−/− mice may be due, at least in part, to less effective co-stimulation between DCs and T cells. In summary, our data suggest that IDO is not required for the induction of airway tolerance, but may play a role in promoting Th2-induced allergic airway disease. Supported by NIH grants HL 77430 (to A.R) and HL60207 (to P.R.)