House dust mite allergen directly activates ILC2 cells via the TLR4 signaling pathway in allergic airway diseases

IF 3.7 4区 医学 Q2 CELL BIOLOGY Cellular immunology Pub Date : 2024-10-18 DOI:10.1016/j.cellimm.2024.104884
{"title":"House dust mite allergen directly activates ILC2 cells via the TLR4 signaling pathway in allergic airway diseases","authors":"","doi":"10.1016/j.cellimm.2024.104884","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Unlike T cells and B cells, the activation process of group 2 innate lymphoid cells (ILC2s) is mainly driven by epithelial cell derived cytokines rather than specific antigen recognition. Whether antigens have a direct role in activating ILC2s remains poorly understood.</div></div><div><h3>Methods</h3><div>Following stimulation, type 2 cytokine secretions and cell death were assessed in house dust mite (HDM)-stimulated ILC2s. To investigate the underlying mechanisms, RNA-sequencing (RNA-seq) was performed on HDM-stimulated ILC2s. The validation experiments were done through <em>in vitro</em> stimulation assays and an HDM-induced asthmatic murine model, using specific inhibitors targeting receptor and relevant proteins of signaling pathways.</div></div><div><h3>Results</h3><div>HDM stimulation increased the secretion of IL-5 and IL-13 cytokines from ILC2s, inhibited apoptosis of ILC2, and promoted the proliferation of ILC2s. As confirmed by RNA-seq, HDM stimulation upregulated genes in ILC2s, including those responsible for type 2 cytokines, ILC2s-specific transcriptional factors, and related receptors. Both toll-like receptor (TLR) 1 and TLR4 were constitutively expressed on ILC2s, however, only TLR4 was predominantly upregulated upon HDM stimulation. TAK242, a specific TLR4 inhibitor, significantly blocked the effect of HDM on ILC2s, in terms of type 2 cytokine secretions and cell death. Using specific inhibitors in pathways, we confirmed that HDM promoted ILC2s activation via TLR4-ERK, p38, and NF-κB signaling pathways.</div></div><div><h3>Conclusions</h3><div>Allergen HDM directly activates ILC2s through TLR4 mediated-ERK/p38/NF-κB signaling pathway. These findings provide new insights into how antigens propagate type 2 immune response via ILC2s, contributing to chronic inflammations in allergic airway diseases.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S000887492400087X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Unlike T cells and B cells, the activation process of group 2 innate lymphoid cells (ILC2s) is mainly driven by epithelial cell derived cytokines rather than specific antigen recognition. Whether antigens have a direct role in activating ILC2s remains poorly understood.

Methods

Following stimulation, type 2 cytokine secretions and cell death were assessed in house dust mite (HDM)-stimulated ILC2s. To investigate the underlying mechanisms, RNA-sequencing (RNA-seq) was performed on HDM-stimulated ILC2s. The validation experiments were done through in vitro stimulation assays and an HDM-induced asthmatic murine model, using specific inhibitors targeting receptor and relevant proteins of signaling pathways.

Results

HDM stimulation increased the secretion of IL-5 and IL-13 cytokines from ILC2s, inhibited apoptosis of ILC2, and promoted the proliferation of ILC2s. As confirmed by RNA-seq, HDM stimulation upregulated genes in ILC2s, including those responsible for type 2 cytokines, ILC2s-specific transcriptional factors, and related receptors. Both toll-like receptor (TLR) 1 and TLR4 were constitutively expressed on ILC2s, however, only TLR4 was predominantly upregulated upon HDM stimulation. TAK242, a specific TLR4 inhibitor, significantly blocked the effect of HDM on ILC2s, in terms of type 2 cytokine secretions and cell death. Using specific inhibitors in pathways, we confirmed that HDM promoted ILC2s activation via TLR4-ERK, p38, and NF-κB signaling pathways.

Conclusions

Allergen HDM directly activates ILC2s through TLR4 mediated-ERK/p38/NF-κB signaling pathway. These findings provide new insights into how antigens propagate type 2 immune response via ILC2s, contributing to chronic inflammations in allergic airway diseases.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
在过敏性气道疾病中,屋尘螨过敏原通过 TLR4 信号通路直接激活 ILC2 细胞。
背景:与 T 细胞和 B 细胞不同,第 2 组先天性淋巴细胞(ILC2s)的活化过程主要由上皮细胞衍生的细胞因子驱动,而非特异性抗原识别。抗原在激活 ILC2s 的过程中是否起直接作用,目前还不十分清楚:方法:在刺激后,评估了家尘螨(HDM)刺激的 ILC2 的 2 型细胞因子分泌和细胞死亡情况。为了研究其潜在机制,对受HDM刺激的ILC2s进行了RNA测序(RNA-seq)。利用针对受体和信号通路相关蛋白的特异性抑制剂,通过体外刺激试验和HDM诱导的哮喘小鼠模型进行了验证实验:结果:HDM刺激增加了ILC2分泌IL-5和IL-13细胞因子,抑制了ILC2的凋亡,促进了ILC2的增殖。RNA-seq证实,HDM刺激上调了ILC2的基因,包括负责2型细胞因子、ILC2特异性转录因子和相关受体的基因。ILC2上的toll样受体(TLR)1和TLR4都是组成型表达的,但在HDM刺激下,只有TLR4主要上调。TLR4特异性抑制剂TAK242能显著阻止HDM对ILC2的影响,包括2型细胞因子的分泌和细胞死亡。通过使用通路中的特异性抑制剂,我们证实了HDM通过TLR4-ERK、p38和NF-κB信号通路促进了ILC2s的活化:结论:过敏原 HDM 可通过 TLR4 介导的 ERK/p38/NF-κB 信号通路直接激活 ILC2。这些发现为了解抗原如何通过 ILC2s 传播 2 型免疫反应、导致过敏性气道疾病中的慢性炎症提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
期刊最新文献
Gastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases Complement system component 3 deficiency modulates the phenotypic profile of murine macrophages Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation House dust mite allergen directly activates ILC2 cells via the TLR4 signaling pathway in allergic airway diseases IL-10: A Key Regulator and potential therapeutic target in uveitis
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1