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

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@article{da5881b30f16477cb0a6dc1014d88fba,
title = "Antagonism of the interleukin 4 receptor α promotes TH 1-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 TH 2 differentiation followed by an upregulation of interferon-γ-producing cells.",
keywords = "Adult, Biomarkers, Cytokines/metabolism, Dermatitis, Atopic/immunology, Female, Humans, Immunoglobulin E/blood, Interleukin-4 Receptor alpha Subunit/antagonists & inhibitors, Leukocytes, Mononuclear/immunology, Male, Middle Aged, Signal Transduction, T-Lymphocyte Subsets/immunology, Th1 Cells/immunology, Young Adult",
author = "Peter Br{\o}gger and Blom, {Lars H} and Stine Simonsen and Thyssen, {Jacob P} and Lone Skov",
note = "{\circledC} 2019 The Scandinavian Foundation for Immunology.",
year = "2020",
month = "1",
doi = "10.1111/sji.12835",
language = "English",
volume = "91",
pages = "e12835",
journal = "Scandinavian Journal of Immunology",
issn = "0300-9475",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Antagonism of the interleukin 4 receptor α promotes TH 1-signalling among T cells from patients with atopic dermatitis after stimulation

AU - Brøgger, Peter

AU - Blom, Lars H

AU - Simonsen, Stine

AU - Thyssen, Jacob P

AU - Skov, Lone

N1 - © 2019 The Scandinavian Foundation for Immunology.

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

KW - Adult

KW - Biomarkers

KW - Cytokines/metabolism

KW - Dermatitis, Atopic/immunology

KW - Female

KW - Humans

KW - Immunoglobulin E/blood

KW - Interleukin-4 Receptor alpha Subunit/antagonists & inhibitors

KW - Leukocytes, Mononuclear/immunology

KW - Male

KW - Middle Aged

KW - Signal Transduction

KW - T-Lymphocyte Subsets/immunology

KW - Th1 Cells/immunology

KW - Young Adult

U2 - 10.1111/sji.12835

DO - 10.1111/sji.12835

M3 - Journal article

VL - 91

SP - e12835

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

SN - 0300-9475

IS - 1

ER -

ID: 58983207