IL-13 x IL-18

Allergic rhinitis (AR) is positively correlated with pyroptosis induced by NLR family pyrin domain containing 3 (NLRP3). Here, the effect of ginsenoside Rg3 on pyroptosis in the progression of AR was evaluated.

Human nasal epithelial cells (HNEPCs) were exposed to house dust mite (HDM) allergen to establish an AR cell model. Cell viability and pyroptosis were tested utilizing CCK-8 and flow cytometry. RT-qPCR and Western blot were used to detect mRNA and protein expression. Co-immunoprecipitation (Co-IP) assay was adopted to validate the molecular interaction. IgE, IL-4, IL-5, IL-13, IL-1β and IL-18 were detected by ELISA. AR mouse model was established using OVA and aluminum hydroxide. The sneezing frequency and nose rubbing frequency of mice were evaluated. HE staining was used to evaluate the pathological changes of nasal mucosa. Pyroptosis was detected by TUNEL and GSDMD staining.

Ginsenoside Rg3 blocked NLRP3 inflammasome activation and pyroptosis induced by HDM allergen in HNEPCs, and increased cell activity inhibited by HDM. SIRT6 depletion overturned the suppressive effect of ginsenoside Rg3 on HDM-caused inflammation and pyroptosis in HNEPCs. Blocking SIRT6 diminished ginsenoside Rg3's protective role against sneezing and rubbing nose, inflammation and pyroptosis in AR mice. Furthermore, Co-IP assay confirmed that SIRT6 interacted with NLRP3 protein in HNEPCs. SIRT6 overexpression could decrease NLRP3 acetylation level and reduce NLRP3 expression.

Our results reveal that ginsenoside Rg3 mitigates AR by controlling NLRP3-triggered inflammatory response and pyroptosis via SIRT6, which provides a new therapeutic strategy for AR treatment.

Ambient fine particulate matter (PM2.5) is believed to be closely connected to asthma severity. However, studies are needed to investigate the underlying mechanism of these findings. Our study attempted to confirm the role of NF-κB/NLRP3 pyroptosis in asthma exacerbation through in vivo and in vitro tests. We also analyzed the differentially expressed genes via RNA-Seq to investigate potential regulatory mechanisms.

We undertook in vivo and in vitro research to investigate the effects of PM2.5 on a mouse asthma model and the human bronchial epithelial cell line Beas-2b. Female BALB/c mice were sensitized with OVA to create a murine asthma model. HE staining and the EMAK system were used to assess airway inflammation and hyperresponsiveness in mouse lungs. We also measured IL-4, IL-5, IL-13, and OVA-specific IgE levels to assess the inflammatory effects of PM2.5 on both normal and OVA-induced asthmatic mice. Western blotting and immunohistochemistry were used to analyze the expression of major NF-κB and pyroptosis proteins. Human bronchial epithelial Beas-2b cells were treated with PM2.5, and the degree of pyroptosis was determined. RNA sequencing (RNA-Seq) was employed to identify differentially expressed genes and investigate potential regulatory mechanisms.

In vivo exposure to PM2.5 significantly increased HE staining scores in a mouse model of asthma. The levels of acetylcholine associated with enhanced airway responsiveness were lower in the PM2.5-exposed asthmatic group than in the control group. Compared with the asthmatic group, the BALF group presented considerably greater levels of IL-1β and IL-18. Compared with those in the asthmatic group, the protein expression levels of NLRP3, Caspase-1, GSDMD-N, cleaved Caspase-1p10, IL-1β, and p-NF-κBp65/NF-κBp65 in the lung tissues of the mice in the PM2.5 group were significantly greater than those in the asthmatic group. In vitro, PM2.5 causes pyroptosis and inflammation in Beas-2B human bronchial epithelial cells via the NF-κB/NLRP3 pathway. The TLR4 inhibitor TAK242 can partially block this effect.

In the OVA-induced asthma mouse model, PM2.5 activates the NF-κB/NLRP3 pathway and induces pyroptosis, thereby exacerbating airway inflammation and hyperreactivity. It may activate the NF-κB signalling cascade through the TLR4/MyD88 pathway, upregulate critical proteins in the pyroptosis pathway, and induce pyroptosis and inflammation in respiratory epithelial Beas-2b cells, exacerbating asthma.

Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood disease classically attributed to innate immune cell dysregulation. This study aimed to elucidate the role of innate lymphoid cells (ILCs), including natural killer (NK) cells and helper‐ILCs (hILCs), in sJIA during clinically inactive disease (CID) through phenotypic and functional analysis.

Peripheral ILCs from children with sJIA during CID receiving interleukin‐1 (IL‐1) inhibitors (n = 40) were analyzed by flow cytometry and compared to 23 healthy children (HC) and 22 patients with unrelated autoinflammatory diseases taking IL‐1 inhibitors. Plasma proteomic profiling was also performed.

Patients with sJIA showed a significant reduction in circulating NK cell frequencies compared to HC, with an increased proportion of CD56bright NK cells. Although overall hILC frequencies were comparable to HC, ILC1s were increased, whereas ILC precursors were reduced. ILC1 frequency correlated positively with IL‐18 plasma levels, whereas ILC2 frequency correlated negatively. Functional assessments revealed that NK cells from patients with sJIA had variable interferon γ (IFNγ) production upon IL‐18/IL‐12 stimulation, inversely correlating with IL‐18 levels. Additionally, hILCs from these patients showed a specific impairment in IFNγ production despite normal IL‐13 production, potentially linked to decreased IL‐18 receptor α expression in ILC1s. Proteomic analysis confirmed IL‐18 as the most up‐regulated cytokine in sJIA plasma.

Patients with sJIA in CID exhibit significant innate immune abnormalities, including altered ILC subset distribution and impaired IFNγ production, strongly associated with IL‐18 levels. These findings suggest ongoing immune dysregulation despite clinical remission, underscoring a potential role for ILCs and cytokine interaction in sJIA pathogenesis.