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Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis

Group 2 innate lymphoid cells (ILCs) are thought to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 stimulates T helper type 2 (Th2) cells and ILC2s to proliferate and produce cytokines. Dupilumab, an antibody against the IL-4 receptor, is used in AD therapy. We speculated that its ef...

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Autores principales: Imai, Yasutomo, Kusakabe, Minori, Nagai, Makoto, Yasuda, Koubun, Yamanishi, Kiyofumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659712/
https://www.ncbi.nlm.nih.gov/pubmed/34909707
http://dx.doi.org/10.1016/j.xjidi.2021.100003
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author Imai, Yasutomo
Kusakabe, Minori
Nagai, Makoto
Yasuda, Koubun
Yamanishi, Kiyofumi
author_facet Imai, Yasutomo
Kusakabe, Minori
Nagai, Makoto
Yasuda, Koubun
Yamanishi, Kiyofumi
author_sort Imai, Yasutomo
collection PubMed
description Group 2 innate lymphoid cells (ILCs) are thought to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 stimulates T helper type 2 (Th2) cells and ILC2s to proliferate and produce cytokines. Dupilumab, an antibody against the IL-4 receptor, is used in AD therapy. We speculated that its efficacy might involve blocking the activation of Th2 cells and ILC2s via IL-4. Here, we examined circulating Th2 cells and ILC2s in 27 Japanese patients with AD before and after the administration of dupilumab. Between 0 and 4 months after dupilumab administration, the percentages of Th2 cells and ILC2s were decreased. Notably, ILC2/3 ratio was decreased after dupilumab treatment. Interestingly, ILC2/3 ratio before dupilumab treatment were significantly higher in high responders than in low responders to dupilumab. To resolve the molecular signatures of the Th2 and ILC2s in AD, we sorted CD4(+) T cells and ILCs from peripheral blood and analyzed their transcriptomes using the BD Rhapsody Single-cell RNA sequencing system. Between 0 and 4 months after dupilumab administration, the Th2 and ILC2 cluster gene signatures were downregulated. Thus, dupilumab might improve dermatitis by suppressing the Th2 cell and ILC2 populations and altering the Th2 and ILC2 repertoire in patients with AD.
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spelling pubmed-86597122021-12-13 Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis Imai, Yasutomo Kusakabe, Minori Nagai, Makoto Yasuda, Koubun Yamanishi, Kiyofumi JID Innov Original Article Group 2 innate lymphoid cells (ILCs) are thought to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 stimulates T helper type 2 (Th2) cells and ILC2s to proliferate and produce cytokines. Dupilumab, an antibody against the IL-4 receptor, is used in AD therapy. We speculated that its efficacy might involve blocking the activation of Th2 cells and ILC2s via IL-4. Here, we examined circulating Th2 cells and ILC2s in 27 Japanese patients with AD before and after the administration of dupilumab. Between 0 and 4 months after dupilumab administration, the percentages of Th2 cells and ILC2s were decreased. Notably, ILC2/3 ratio was decreased after dupilumab treatment. Interestingly, ILC2/3 ratio before dupilumab treatment were significantly higher in high responders than in low responders to dupilumab. To resolve the molecular signatures of the Th2 and ILC2s in AD, we sorted CD4(+) T cells and ILCs from peripheral blood and analyzed their transcriptomes using the BD Rhapsody Single-cell RNA sequencing system. Between 0 and 4 months after dupilumab administration, the Th2 and ILC2 cluster gene signatures were downregulated. Thus, dupilumab might improve dermatitis by suppressing the Th2 cell and ILC2 populations and altering the Th2 and ILC2 repertoire in patients with AD. Elsevier 2021-02-20 /pmc/articles/PMC8659712/ /pubmed/34909707 http://dx.doi.org/10.1016/j.xjidi.2021.100003 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Imai, Yasutomo
Kusakabe, Minori
Nagai, Makoto
Yasuda, Koubun
Yamanishi, Kiyofumi
Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis
title Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis
title_full Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis
title_fullStr Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis
title_full_unstemmed Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis
title_short Dupilumab Effects on Innate Lymphoid Cell and Helper T Cell Populations in Patients with Atopic Dermatitis
title_sort dupilumab effects on innate lymphoid cell and helper t cell populations in patients with atopic dermatitis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659712/
https://www.ncbi.nlm.nih.gov/pubmed/34909707
http://dx.doi.org/10.1016/j.xjidi.2021.100003
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