Antagonism of the interleukin 4 receptor α promotes TH1-signalling among T cells from patients with atopic dermatitis after stimulation

Abstract

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease. Molecular characterization of AD shows an underlying inflammation with tissue infiltration of T helper (TH) 2 cells and increased IL-4 and IL-13. The multifaceted roles of IL-4 and IL-13 in allergic disease development make IL-4Rα an attractive target for treatment strategies, and a neutralizing monoclonal antibody which antagonizes the effects of both IL-4 and IL-13 by blocking the interaction site found in the IL-4 receptor subunit α (IL-4Rα) has been successfully used to treat patients with moderate-to-severe AD. To elucidate the effects of IL-4Rα blockade on the cellular level, we used flow cytometry to examine cytokine production after antigen stimulation in human T cells from patients with AD (n = 12) and healthy controls (n = 6). The cells were stimulated with and without a neutralizing monoclonal antibody against IL-4Rα. Our results indicate that blocking IL-4Rα prohibits IL-4 signalling and IL-13 signalling and thereby TH2 differentiation followed by an upregulation of interferon-γ-producing cells.