CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice

Abstract Atopic dermatitis (AD) patients with skin barrier dysfunction are considered to be at a higher risk of allergic contact dermatitis (ACD), although previous studies showed that attenuated ACD responses to strong sensitizers in AD patients compared to healthy controls. However, the mechanisms...

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Main Authors: Hiroe Tetsu, Kanako Nakayama, Taku Nishijo, Takuo Yuki, Masaaki Miyazawa
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-35139-y
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author Hiroe Tetsu
Kanako Nakayama
Taku Nishijo
Takuo Yuki
Masaaki Miyazawa
author_facet Hiroe Tetsu
Kanako Nakayama
Taku Nishijo
Takuo Yuki
Masaaki Miyazawa
author_sort Hiroe Tetsu
collection DOAJ
description Abstract Atopic dermatitis (AD) patients with skin barrier dysfunction are considered to be at a higher risk of allergic contact dermatitis (ACD), although previous studies showed that attenuated ACD responses to strong sensitizers in AD patients compared to healthy controls. However, the mechanisms of ACD response attenuation in AD patients are unclear. Therefore, using the contact hypersensitivity (CHS) mouse model, this study explored the differences in CHS responses to hapten sensitization between NC/Nga mice with or without AD induction (i.e., non-AD and AD mice, respectively). In this study, ear swelling and hapten-specific T cell proliferation were significantly lower in AD than in non-AD mice. Moreover, we examined the T cells expressing cytotoxic T lymphocyte antigen-4 (CTLA-4), which is known to suppress T cell activation, and found a higher frequency of CTLA-4+ regulatory T cells in draining lymph node cells in AD than in non-AD mice. Furthermore, the blockade of CTLA-4 using a monoclonal antibody eliminated the difference in ear swelling between non-AD and AD mice. These findings suggested that CTLA-4+T cells may contribute to suppressing the CHS responses in AD mice.
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spelling doaj.art-ac983f52474d47398f2d8ee1a85f2aa02023-07-02T11:13:31ZengNature PortfolioScientific Reports2045-23222023-05-011311910.1038/s41598-023-35139-yCTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model miceHiroe Tetsu0Kanako Nakayama1Taku Nishijo2Takuo Yuki3Masaaki Miyazawa4Safety Science Research Laboratories, Kao CorporationSafety Science Research Laboratories, Kao CorporationSafety Science Research Laboratories, Kao CorporationSafety Science Research Laboratories, Kao CorporationSafety Science Research Laboratories, Kao CorporationAbstract Atopic dermatitis (AD) patients with skin barrier dysfunction are considered to be at a higher risk of allergic contact dermatitis (ACD), although previous studies showed that attenuated ACD responses to strong sensitizers in AD patients compared to healthy controls. However, the mechanisms of ACD response attenuation in AD patients are unclear. Therefore, using the contact hypersensitivity (CHS) mouse model, this study explored the differences in CHS responses to hapten sensitization between NC/Nga mice with or without AD induction (i.e., non-AD and AD mice, respectively). In this study, ear swelling and hapten-specific T cell proliferation were significantly lower in AD than in non-AD mice. Moreover, we examined the T cells expressing cytotoxic T lymphocyte antigen-4 (CTLA-4), which is known to suppress T cell activation, and found a higher frequency of CTLA-4+ regulatory T cells in draining lymph node cells in AD than in non-AD mice. Furthermore, the blockade of CTLA-4 using a monoclonal antibody eliminated the difference in ear swelling between non-AD and AD mice. These findings suggested that CTLA-4+T cells may contribute to suppressing the CHS responses in AD mice.https://doi.org/10.1038/s41598-023-35139-y
spellingShingle Hiroe Tetsu
Kanako Nakayama
Taku Nishijo
Takuo Yuki
Masaaki Miyazawa
CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice
Scientific Reports
title CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice
title_full CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice
title_fullStr CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice
title_full_unstemmed CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice
title_short CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice
title_sort ctla 4 suppresses hapten induced contact hypersensitivity in atopic dermatitis model mice
url https://doi.org/10.1038/s41598-023-35139-y
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