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Re-exposure to a relevant skin allergen initiates the efferent phase and clinical expression of allergic contact dermatitis (ACD) characterized by local DC-mediated T cell activation and recruitment of Ag-specific T cells to the sites of allergen challenge. We here made the novel observation that, in contrast to non-lesional skin of ACD patients, skin of (+) patch-tested individuals (effector phase of ACD) showed high expression of IL-15 in epidermal keratinocytes and in dermal DC-macrophage-T cell-clusters. Interestingly, within these clusters, T cells with increased anti-apoptotic BCL2 were found directly adjacent to IL-27-producing CD14+ CD86+ CD172a+ cells and IL-15+ cells. Moreover, in the allergic contact hypersensitivity (CHS) model using IL-27p28 eGFP mice, we found increased IL-27 production in a distinct macrophage subset expressing CD172a. Functionally, IL-27 conditional knockout mice (driven by …