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J Invest Dermatol ; 141(8): 1943-1953.e13, 2021 08.
Article in English | MEDLINE | ID: mdl-33610558

ABSTRACT

Dupilumab, a mAb targeting IL-4 receptor alpha (IL-4Rα), markedly improves disease severity in patients with atopic dermatitis. However, the effect of IL-4Rα 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-4Rα 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-4Rα 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 cytokine-producing 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-4Rα, 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.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Dermatitis, Atopic/drug therapy , T-Lymphocytes/drug effects , Adult , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Dermatitis, Atopic/blood , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/immunology , Drug Administration Schedule , Female , Humans , Injections, Subcutaneous , Interleukin-4 Receptor alpha Subunit/antagonists & inhibitors , Interleukin-4 Receptor alpha Subunit/metabolism , Male , Middle Aged , Severity of Illness Index , Skin/cytology , Skin/immunology , Skin/pathology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Treatment Outcome
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