Antagonism of the interleukin 4 receptor α promotes TH 1-signalling among T cells from patients with atopic dermatitis after stimulation

Scand J Immunol. 2020 Jan;91(1):e12835. doi: 10.1111/sji.12835. Epub 2019 Nov 3.

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 TH 2 differentiation followed by an upregulation of interferon-γ-producing cells.

Keywords: CD4; IL4Rα; T helper cells; atopic dermatitis; dupilumab.

MeSH terms

  • Adult
  • Biomarkers
  • Cytokines / metabolism
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / metabolism*
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Interleukin-4 Receptor alpha Subunit / antagonists & inhibitors*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • IL4R protein, human
  • Interleukin-4 Receptor alpha Subunit
  • Immunoglobulin E

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