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Re-exposure to an allergen (Ag) initiates the efferent phase and clinical expression of allergic contact dermatitis (ACD) characterized by recruitment of Ag-specific T cells to the sites of Ag challenge. We observed that, in contrast to non-lesional skin of ACD patients, skin of (+) patch-tested individuals showed high expression of IL-15 in keratinocytes, and in monocyte/macrophage (MAC) within dermal hair follicle (HF)-associated immune cell clusters. Within these clusters, T cells with high BCL2 interacted with CD14+ cells co-expressing IL-15 and iNOS and/or CD86 and IL-27. Moreover, in the murine allergic contact hypersensitivity (CHS) model using IL-27p28 eGFP mice, we found increased IL-27 production in CD172a+ MAC. Functionally, IL-27p28fl/fl; LysM-cre mice demonstrated less DNFB-induced ear thickening and dermal HF-associated CD8 T cells compared to WT mice (p< 0.05), supporting a functional …