Early and Long-Term Effects of Dupilumab Treatment on Circulating T-Cell Functions in Patients with Moderate-to-Severe Atopic Dermatitis

Dupilumab, a mAb targeting IL-4 receptor alpha (IL-4R alpha), markedly improves disease severity in patients with atopic dermatitis. However, the effect of IL-4R alpha blockade on dynamics of circulating skin-homing T cells, which are crucial players in the pathologic mechanism of atopic dermatitis, has not been studied yet. In addition, it remains unknown whether dupilumab treatment induces long-lasting T- and B-cell polarization. Therefore, we studied the short- and long-term effects of dupilumab treatment on IL-4R alpha expression and T-cell cytokine production within total and skin-homing (cutaneous lymphocyte antigen(+)/CCR4(+)) subpopulations in patients with moderate-to-severe atopic dermatitis. Dupilumab treatment completely blocked IL-4R alpha expression and signal transducer and activator of transcription 6 phosphorylation in CD19(+) B cells and CD4(+) T cells within 2 hours of administration and through week 52. Although no change in the proportion of skin-homing T-cell subsets was found, dupilumab treatment significantly decreased the percentage of proliferating (Ki67(+)) and T helper type 2 and T helper type 22 cytokineeproducing skin-homing CD4(+) T cells at week 4. No evidence of general T helper type cell skewing following a year of dupilumab treatment was found. In summary, dupilumab treatment rapidly and stably inhibited IL-4R alpha, which was accompanied by a strong early functional immunological effect specifically on skin-homing T cells without affecting overall T helper type cell skewing in the long term.