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

J Invest Dermatol. 2021 Aug;141(8):1943-1953.e13. doi: 10.1016/j.jid.2021.01.022. Epub 2021 Feb 18.


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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Dermatitis, Atopic / blood
  • Dermatitis, Atopic / diagnosis
  • Dermatitis, Atopic / drug therapy*
  • 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 / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • IL4R protein, human
  • Interleukin-4 Receptor alpha Subunit
  • dupilumab