2. Academic Validation
  3. House dust mite allergen directly activates ILC2 cells via the TLR4 signaling pathway in allergic airway diseases

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

  • Cell Immunol. 2024 Oct 18:405-406:104884. doi: 10.1016/j.cellimm.2024.104884.
Yan Li 1,  Zhennan Qu 1,  Xue Wang 1,  Qiqi Wang 1,  Zhe Lv 2,  Wei Wang 2,  Sun Ying 2,  Luo Zhang 3,  Feng Lan 4
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing 100005, China; Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100005, China.
  • 2 Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
  • 3 Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing 100005, China; Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address: dr.luozhang@139.com.
  • 4 Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing 100005, China; Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address: fenglanent@126.com.
PMID: 39437527 DOI: 10.1016/j.cellimm.2024.104884
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.

Keywords

Allergic airway diseases; Group 2 innate lymphoid cell; House dust mite; Toll-like receptor 4.

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