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Background: Pathogenesis of atopic dermatitis (AD) involves interaction between type 2 cells that include basophils, mast cells, innate lymphoid type 2 cells (ILC2), and Th2 cells. Levels of IL-4 and IL-13 are elevated in AD patients. Objective: Here, we investigated the distribution of type 2 cells and the source of IL-4 and IL-13 in skin and blood of AD relative to psoriasis. Methods: Lesional skin biopsies and blood were collected from patients. Skin cell suspensions were prepared by mild enzymatic digestion and mechanical dissociation. IL-4 and IL-13 expression was analyzed at single-cell level before or after stimulation using flow cytometry. Results: Frequencies of basophils, ILC2 and Th2 but not mast cells were significantly elevated in skin, and not blood, of AD relative to psoriasis. IL-4 production by circulating basophils and Th2 cells, and IL-13 by ILCs and Th2 cells was similar in both diseases. In contrast, skin T cells expressed IL-4 and IL-13 prior to stimulation in AD when compared to psoriasis. Moreover, skin basophils, which were detected in AD only, expressed IL-4 following stimulation. Interestingly, basophils and ILC2 were positively correlated in skin, whereas skin basophils were inversely correlated with blood ILC2. Conclusions: Lesional AD skin harbors a distinctive innate and adaptive type 2 profile, which is characterized by basophils producing IL-4, Th2 cells expressing IL-4 or IL-13, and ILC2. This underlies the therapeutic efficacy of targeting IL-4 and IL-13 signaling pathways in AD.

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