CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses

Allergic rhinitis (AR) is an immunoglobulin E-mediated type 2 inflammation of the nasal mucosa that is mainly driven by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). CD226 is a costimulatory molecule associated with inflammatory response and is mainly expressed on T cells, na...

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Main Authors: Yang Xie, Yuan Zhang, Tianxiao Zhu, Jingchang Ma, Chujun Duan, Lu Yang, Tingting Wang, Ran Zhuang, Ka Bian, Lianjun Lu
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2022/1756395
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author Yang Xie
Yuan Zhang
Tianxiao Zhu
Jingchang Ma
Chujun Duan
Lu Yang
Tingting Wang
Ran Zhuang
Ka Bian
Lianjun Lu
author_facet Yang Xie
Yuan Zhang
Tianxiao Zhu
Jingchang Ma
Chujun Duan
Lu Yang
Tingting Wang
Ran Zhuang
Ka Bian
Lianjun Lu
author_sort Yang Xie
collection DOAJ
description Allergic rhinitis (AR) is an immunoglobulin E-mediated type 2 inflammation of the nasal mucosa that is mainly driven by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). CD226 is a costimulatory molecule associated with inflammatory response and is mainly expressed on T cells, natural killer cells, and monocytes. This study is aimed at elucidating the role of CD226 in allergic inflammatory responses in murine AR using global and CD4+ T cell-specific Cd226 knockout (KO) mice. AR nasal symptoms were assessed based on the frequency of nose rubbing and sneezing. Hematoxylin and eosin and periodic acid–Schiff staining and quantitative real-time PCR methods were used to determine eosinophils, goblet cells, and ILC2-associated mRNA levels in the nasal tissues of mice. CD226 levels on ILC2s were detected using flow cytometry, and an immunofluorescence double staining assay was employed to determine the number of ILC2s in the nasal mucosa. The results showed that global Cd226 KO mice, but not CD4+ T cell-specific Cd226 KO mice, exhibited attenuated AR nasal symptoms. Eosinophil recruitment, goblet cell proliferation, and Th2-inflammatory cytokines were significantly reduced, which resulted in the alleviation of allergic and inflammatory responses. ILC2s in the murine nasal mucosa expressed higher levels of CD226 after ovalbumin stimulation, and CD226 deficiency led to a reduction in the proportion of nasal ILC2s and ILC2-related inflammatory gene expression. Hence, the effect of CD226 on the AR mouse model may involve the regulation of ILC2 function rather than CD4+ T cells.
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spelling doaj-art-bf87ba5789d54e01aef1c85c92c486cf2025-02-03T06:12:57ZengWileyMediators of Inflammation1466-18612022-01-01202210.1155/2022/1756395CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell ResponsesYang Xie0Yuan Zhang1Tianxiao Zhu2Jingchang Ma3Chujun Duan4Lu Yang5Tingting Wang6Ran Zhuang7Ka Bian8Lianjun Lu9Department of OtorhinolaryngologyInstitute of Medical ResearchDepartment of PeriodontologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of ImmunologyDepartment of OtorhinolaryngologyDepartment of OtorhinolaryngologyAllergic rhinitis (AR) is an immunoglobulin E-mediated type 2 inflammation of the nasal mucosa that is mainly driven by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). CD226 is a costimulatory molecule associated with inflammatory response and is mainly expressed on T cells, natural killer cells, and monocytes. This study is aimed at elucidating the role of CD226 in allergic inflammatory responses in murine AR using global and CD4+ T cell-specific Cd226 knockout (KO) mice. AR nasal symptoms were assessed based on the frequency of nose rubbing and sneezing. Hematoxylin and eosin and periodic acid–Schiff staining and quantitative real-time PCR methods were used to determine eosinophils, goblet cells, and ILC2-associated mRNA levels in the nasal tissues of mice. CD226 levels on ILC2s were detected using flow cytometry, and an immunofluorescence double staining assay was employed to determine the number of ILC2s in the nasal mucosa. The results showed that global Cd226 KO mice, but not CD4+ T cell-specific Cd226 KO mice, exhibited attenuated AR nasal symptoms. Eosinophil recruitment, goblet cell proliferation, and Th2-inflammatory cytokines were significantly reduced, which resulted in the alleviation of allergic and inflammatory responses. ILC2s in the murine nasal mucosa expressed higher levels of CD226 after ovalbumin stimulation, and CD226 deficiency led to a reduction in the proportion of nasal ILC2s and ILC2-related inflammatory gene expression. Hence, the effect of CD226 on the AR mouse model may involve the regulation of ILC2 function rather than CD4+ T cells.http://dx.doi.org/10.1155/2022/1756395
spellingShingle Yang Xie
Yuan Zhang
Tianxiao Zhu
Jingchang Ma
Chujun Duan
Lu Yang
Tingting Wang
Ran Zhuang
Ka Bian
Lianjun Lu
CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses
Mediators of Inflammation
title CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses
title_full CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses
title_fullStr CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses
title_full_unstemmed CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses
title_short CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses
title_sort cd226 deficiency alleviates murine allergic rhinitis by suppressing group 2 innate lymphoid cell responses
url http://dx.doi.org/10.1155/2022/1756395
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