066 Glucocorticoids promote intrinsic human Th17 differentiation

Abstract

Contact hypersensitivity (CHS) is a mouse model for human allergic contact dermatitis (ACD). Although human ACD lesions are frequently characterized by a mixed gene expression pattern of Th1 IFN-g and Th2 IL-4, a majority of murine CHS studies induced by strong model haptens have heavily focused on the role of Th1 IFN-g. Here, we found that oxazolone (Ox)-induced CHS model showed a mixed gene expression signature of IFN-g and IL-4, and type 2 cytokine IL-4 was associated with the severity of skin inflammation. Ox-induced lesional CHS skins demonstrated an increased gene expression level of cytokines and chemokines which belong to both Th1 and Th2 immunities. During the sensitization phase, IL-4 mRNA expression was markedly increased in the skin-draining lymph nodes at 72hr after a single topical application of Ox. The extent of ear thickness and transcript level of IL-4 were significantly lower in mice depleted with LangerineCD301bþ dermal dendritic cells (DCs), whereas local expression of IFN-g was comparable to that of control mice. Interestingly, Ox-induced CHS responses and local gene expression of IL-4 was not affected after by depletion of all Langerinþ DC subsets in the skin. Therefore, our findings suggest a novel insight for the possible role of type 2 immunity in Ox-induced CHS model, which is mediated by a specific subset of CD301bþ dermal dendritic cells in the skin.