The IL-37–Mex3B–Toll-like receptor 3 axis in epithelial cells in patients with eosinophilic chronic rhinosinusitis with nasal polyps

Liu, Jinxin; Liao, Bo; Yu, Qihong; Wang, Hai; Liu, Yibo; Guo, Chongfeng; Wang, Zhichao; Li, Zhiyong; Wang, Zhe-Zheng; Ruan, Jian-Wen; Li, Pan; Yao, Yin; Chen, Cailing; Wang, Heng; Liang, Yucheng; Zhen, Guohua; Liu, Zheng

doi:10.1016/j.jaci.2019.07.009

Cited by 30 publications

(53 citation statements)

References 51 publications

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“…In this issue of The Journal of Allergy and Clinical Immunology, the report published by Liu et al 6 points to an important role of IL-37 in CRSsNP and eosinophilic and noneosinophilic CRSwNP. The authors convincingly demonstrated the expression of IL-37 in nasal tissues and scraped nasal epithelial cells from patients with CRS.…”

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confidence: 98%

“…The reduced IL-37 secretion in eosinophilic CRSwNP could be a consequence of reduced infiltration of macrophages, mast cells, and T and B cells that are known to produce IL-37 as well. Unfortunately, Liu et al 6 did not exclude this possibility.…”

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confidence: 99%

“…Liu et al 6 studied the regulation of IL-37 expression following its stimulation with a broad spectrum of different agents. Surprisingly, several tested stimuli such as TLR agonists, T H 1, T H 2, and T H 17 cytokines, were able to upregulate IL-37 at both mRNA and protein levels.…”

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confidence: 99%

“…Using a transcriptomics approach in epithelial cells derived from patients with eosinophilic CRSwNP, Liu et al 6 identified a list of genes differentially expressed upon IL-37 treatment. Among these genes, Mex3 RNA-binding protein (Mex3B) showed a 3-fold decrease in the IL-37treated group compared with the control.…”

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confidence: 99%

“…In this way, the observed effect of attenuated TLR3 signaling in an IL-37-rich microenvironment should be noticeable in patients who present evidence only of sufficient viral presence. Despite some missing links, Liu et al 6 have performed an enormous amount of work, which represents an important input for our understanding of the role of IL-37 in CRS. Furthermore, additional data were provided for other T H 2-driven human diseases, such as allergic rhinitis and eosinophilic asthma, as well as for an in vivo experimental mouse model.…”

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confidence: 99%

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IL-37: A new player in the chronic rhinosinusitis arena

Markov

Simon

2020

Journal of Allergy and Clinical Immunology

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confidence: 98%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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IL-37: A new player in the chronic rhinosinusitis arena

Markov

Simon

2020

Journal of Allergy and Clinical Immunology

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sPLA2GIB Promotes PGD2 and IL‐13 Production in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

Kang,

Liu,

et al. 2023

The Laryngoscope

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ObjectiveSecreted phospholipase A2 Group IB (sPLA2GIB) regulates the release of arachidonic acid, prostaglandins, and other inflammatory lipid mediators. Although it has been well involved in extensive inflammatory diseases, its specific mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. In this study, we investigated the role of sPLA2GIB in the pathophysiology of CRSwNP.MethodsQuantitative PCR, immunofluorescence staining, western blotting, and enzyme‐linked immunosorbent assay (ELISA) were used to analyze the expression of sPLA2s, phospholipase A2 receptor (PLA2R), and prostaglandin D2 (PGD2) in nasal samples. Human nasal epithelial cells (HNECs) were cultured at an air‐liquid interface (ALI) and stimulated with various cytokines. The human mast cell line HMC‐1 was stimulated with sPLA2GIB, and the expression of PGD2 and cytokines in the culture supernatant was detected by ELISA.ResultsThe mRNA and protein levels of sPLA2GIB were significantly higher in eosinophilic CRSwNP than in control tissues. sPLA2GIB was predominantly expressed in the nasal epithelial cells. PLA2R mRNA and protein levels were upregulated in both eosinophilic and non‐eosinophilic CRSwNP compared with the control groups. IL‐4, IL‐13, TNF‐α, and IL‐1β upregulated the expression of sPLA2GIB in ALI‐cultured HNECs. sPLA2GIB induced PGD2 and IL‐13 production in HMC‐1 cells in a hydrolytic activity‐independent manner. PGD2 protein expression was elevated in tissue homogenates of eosinophilic CRSwNP, and PGD2 upregulated the expression of IL‐13 in HMC‐1 cells.ConclusionIncreased secretion of sPLA2GIB by epithelial cells may promote eosinophilic inflammation in CRSwNP by enhancing PGD2 and IL‐13 production in mast cells via binding to PLA2R.Level of EvidenceN/A Laryngoscope, 2023

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Endoplasmic reticulum stress promotes local immunoglobulin E production in allergic rhinitis

Liu

Zhen

Chen

et al. 2021

Laryngoscope Investig Oto

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Background The role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive. Methods Real‐time polymerase chain reaction (RT‐PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78‐kDa glucose‐regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X‐box binding protein 1 (sXBP‐1), and phosphorylated eukaryotic initiation factor 2α (p‐eIF2α), in inferior turbinate tissue samples from patients with AR and non‐AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4‐phenylbutyric acid (4‐PBA), an ER stress inhibitor. Results Compared to those in non‐AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non‐AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4‐PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α was significantly reduced in cultured AR‐derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants. Conclusions ER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production. Level of Evidence NA

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The IL-37–Mex3B–Toll-like receptor 3 axis in epithelial cells in patients with eosinophilic chronic rhinosinusitis with nasal polyps

Cited by 30 publications

References 51 publications

IL-37: A new player in the chronic rhinosinusitis arena

IL-37: A new player in the chronic rhinosinusitis arena

sPLA2GIB Promotes PGD2 and IL‐13 Production in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

Endoplasmic reticulum stress promotes local immunoglobulin E production in allergic rhinitis

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