γδT cells contribute to type 2 inflammatory profiles in eosinophilic chronic rhinosinusitis with nasal polyps

2019 ◽  
Vol 133 (22) ◽  
pp. 2301-2315 ◽  
Author(s):  
Xia Li ◽  
Zhiyuan Wang ◽  
Lihong Chang ◽  
Xiaohong Chen ◽  
Luoying Yang ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Murine Model ◽  
Inflammatory Markers ◽  
Nasal Polyps ◽  
Γδt Cells ◽  
Control Subjects ◽  
Nasal Tissue ◽  
Type 2 Cytokines ◽  
Eosinophilic Chronic Rhinosinusitis

Abstract Eosinophilic chronic rhinosinusitis with nasal polyps (ECRS) is a condition linked with type 2 inflammation, poor treatment outcomes, and high recurrence tendency. Although γδT cells have been reported to induce type 2 immune responses and eosinophilic infiltration in several diseases, their role in ECRS has not been fully explored. We aimed to evaluate the association of γδT cells with the type 2 inflammatory profiles in ECRS. Nasal tissue samples obtained from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (51 eosinophilic and 48 non-eosinophilic), 50 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 58 control subjects were examined for γδT cells, inflammatory markers and eosinophils using HE, RT-qPCR, ELISA, immunofluorescence, and flow cytometry. In parallel, studies were also conducted in an ECRS murine model induced by anti-γδT cells neutralizing antibody administration. γδT cells expression was significantly increased in tissues from patients with ECRS compared with non-ECRS, CRSsNP and control subjects. Moreover, inflammatory markers including type 2 proinflammatory cytokines (IL-4, IL-5, IL-13), GATA3, eosinophil cationic protein (ECP), and eotaxin levels were also increased in nasal tissues of patients with ECRS, and Vγ1+ γδT cells mRNA expression was positively correlated with type 2 cytokines, GATA3, and ECP. In the ECRS murine model, anti-Vγ1+ γδT antibody treatment reduced the infiltration of eosinophils and expression of type 2 cytokines, GATA3, and ECP in nasal mucosae. In conclusion, the results of the present study suggest that γδT cells play a crucial role in the type 2 inflammatory profiles and nasal tissue eosinophilic infiltration in patients with ECRS.

scholarly journals Chronic Rhinosinusitis with Nasal Polyps: Age and Disease Severity Differences in the Levels of Inflammatory Markers

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 282
Author(s):  
Justinas Vaitkus ◽  
Astra Vitkauskienė ◽  
Regimantas Simuntis ◽  
Žygimantas Vaitkus ◽  
Nora Šiupšinskienė ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Inflammatory Markers ◽  
Nasal Polyps ◽  
Clinical Symptoms ◽  
Age Groups ◽  
Magnetic Bead ◽  
Control Group ◽  
Control Subjects ◽  
Nasal Tissue ◽  
And Control

Background and objectives: The aim of our study was to analyze the concentrations of inflammatory markers in the nasal tissue of patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls of different age groups, as well as to find associations between age, inflammation development, and NPs. Materials and methods: Patients were divided into two groups—patients with CRSwNPs and control subjects who had nasal surgery for another reason beside CRS. Our analysis was performed across three different age groups (18–30 years, 31–50 years, and 51 years and more). Tissue biopsies from the sinus cavity for all study participants were taken and frozen at −80 °C, until use. The concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IL-21, and IL-22, were quantified using a magnetic bead-based multiplex assay. Results: In the group aged 18–30 years, the levels of inflammatory markers IL-1, IL-2, IL-5, and IL-22 were significantly higher in patients with CRSwNPs than the control subjects. Among patients aged 31–50 years, significantly higher concentrations of IL-2, IL-4, IL-5, and IL-22 were recorded in patients with CRSwNPs, as compared to the control subjects. In the oldest group (aged 51 years and more), patients with CRSwNPs had significantly higher concentrations of IL-2, IL-4, and IL-22, as compared to the control group. In the CRSwNP group, only the concentration of IL-21 was significantly higher among patients aged 31–50 years, as compared with those aged 51 years and older (p = 0.013). Conclusions: IL-2 and IL-22 levels were significantly higher in patients with CRSwNP than the control, across all age groups. Only the concentration of IL-21 was higher among patients with CRSwNP in the middle age group, as compared to the oldest group. IL-2, IL-4, and IL-22 levels correlated with the severity of CRSwNPs. Elevated concentrations of IL-2, IL-4, and IL-22 were determined in patients’ groups with higher sinonasal outcome test (SNOT-22) scores, pointing to more severe clinical symptoms.

scholarly journals Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Monica Boita ◽  
Caterina Bucca ◽  
Giuseppe Riva ◽  
Enrico Heffler ◽  
Giovanni Rolla
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Cell Cultures ◽  
Nasal Polyps ◽  
Dermatophagoides Pteronyssinus ◽  
Poly I:C ◽  
Type 2 Cytokines ◽  
Sinus Mucosa

Background. T2 inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) may be influenced by epithelial cytokines release (TSLP, IL-25, and IL-33). We investigated the release of TSLP, IL-25, and IL-33 by epithelial CRSwNP cells compared to epithelial sinus mucosa cells of patients with chronic rhinosinusitis without nasal polyps (CRSsNP).Methods. IL-25, IL-33, and TSLP were measured by ELISA in the supernatant of cell cultures derived by CRSwNP (9 patients, 6 atopic) and CRSsNP (7 patients, 2 atopic) in baseline condition and following stimulation withDermatophagoides pteronyssinus(DP),Aspergillus fumigatus(AF), and poly(I:C).Results. CRSwNP epithelial cells released increased levels of IL-25 (from 0.12 ± 0.06 pg/ml to 0.27 ± 0.1 pg/ml,p<0.01) and TSLP (from 0.77 ± 0.5 pg/ml to 2.53 ± 1.17 pg/ml,p<0.001) following poly(I:C) stimulation, while CRSsNP epithelial cells released increased levels of IL-25 and IL-33 following AF and DP stimulation, respectively (IL-25: from 0.18 ± 0.07 pg/ml to 0.51 ± 0.1 pg/ml,p<0.001; IL-33: from 2.57 ± 1.3 pg/ml to 5.7 ± 3.1 pg/ml,p<0.001).Conclusions. CRSwNP epithelial cells release TSLP and IL-25 when stimulated by poly(I:C) but not by DP or AF, suggesting that viral infection may contribute to maintain and amplify the T2 immune response seen in CRSwNP.

scholarly journals Upregulation of Basonuclin1 Is Associated with p63-Involved Epithelial Barrier Impairment and Type-2 Helper T-cell Inflammation in Chronic Rhinosinusitis with Nasal Polyps

2021 ◽  
pp. 1-12
Author(s):  
Yunbo Gao ◽  
Jingyun Li ◽  
Jian Jiao ◽  
Ying Li ◽  
Chengshuo Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Mrna Level ◽  
Mucosal Inflammation ◽  
Epithelial Barrier ◽  
Helper T Cell ◽  
Downstream Target ◽  
Nasal Tissue

<b><i>Background:</i></b> Tumor protein p63 has been shown to be important for epithelial dysfunction, including epithelial barrier defects and mucosal inflammation, in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Basonuclin1 (BNC1), an epithelial-specific transcriptional factor, is a direct downstream target of p63 and thus might be involved in the pathogenesis of CRSwNP. <b><i>Objective:</i></b> We sought to investigate whether BNC1 was associated with p63-mediated epithelial barrier defects and nasal mucosal inflammation in CRSwNP. <b><i>Methods:</i></b> Nasal tissue biopsies were obtained from 91 patients to CRSwNP, 49 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 28 control subjects. Immunohistochemistry and immunofluorescence staining were used to determine the distribution of BNC1 in tissues and localization in cells, respectively. Quantitative PCR was performed to detect the expression levels of <i>BNC1</i>, <i>TP63</i>, epithelial barrier proteins, and type-2 helper T-cell inflammation-related genes. <b><i>Results:</i></b> <i>BNC1</i> mRNA expression was significantly elevated in the tissues in CRSwNP patients compared with CRSsNP (1.96-fold, <i>p</i> = 0.0003) and control groups (2.40-fold, <i>p</i> &#x3c; 0.0001). <i>BNC1</i> staining was strongly positive in the nasal epithelium and co-localized with p63-positive epithelial cells. The expression of <i>BNC1</i> mRNA was strongly correlated with <i>TP63</i> mRNA level both in tissue biopsies (<i>r</i> = 0.78, <i>p</i> &#x3c; 0.0001) and epithelial scrapings (<i>r</i> = 0.97, <i>p</i> &#x3c; 0.0001). <i>BNC1</i> expression was also positively correlated with epithelial barrier protein genes (<i>CDH1</i>, <i>CLDN1</i>, <i>CLDN4</i>, <i>TJP1,</i> and <i>TJP2</i>) and epithelial genes involved in T<sub>H</sub>2 inflammation (<i>IL33</i>, <i>CCL26</i>, <i>CLC</i>, and <i>ALOX15</i>). <b><i>Conclusions:</i></b> Overexpression of <i>BNC1</i> may be associated with increased expression of <i>TP63</i>, and possibly contribute to the epithelial barrier defects and T<sub>H</sub>2 inflammation in CRSwNP.

Increased Expression of TXNIP Facilitates Oxidative Stress in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis With Nasal Polyps

2020 ◽  
pp. 194589242098241
Author(s):  
Hai Lin ◽  
Guangyi Ba ◽  
Ru Tang ◽  
Mingxian Li ◽  
Zhipeng Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Real Time ◽  
Chronic Rhinosinusitis ◽  
Western Blotting ◽  
Real Time Pcr ◽  
Nasal Polyps ◽  
Sod Activity ◽  
Nasal Tissue ◽  
Sod Assay

Background Oxidative stress plays crucial roles in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Thioredoxin-interacting protein (TXNIP) is essential in the process of triggering oxidative stress. However, its role and mechanism in CRSwNP remain unclear. The present study sought to explore the role and mechanism of TXNIP in the pathogenesis of CRSwNP. Methods Western blotting, real-time PCR and immunohistochemistry (IHC) were employed to assess TXNIP, thioredoxin (TRX) expression in nasal tissue samples from patients with CRSwNP and control subjects. MDA level and SOD activity in nasal tissue homogenates were measured using MDA and SOD Assay Kit. To evaluate the role and mechanism of TXNIP in CRSwNP, human nasal epithelial cells (HNECs) were cultured and stimulated using TXNIP siRNA, with or without N-acetylcysteine (NAC, an ROS scavenger). Western blotting, real-time PCR, ROS detecting dye DCFH-DA, MDA and SOD Assay Kit were performed to assess the effects and mechanisms of stimulators on the cells. Results We found significantly increased levels of TXNIP and decreased levels of TRX protein, mRNA, positive cells, increased MDA level and decreased SOD activity in CRSwNP patients compared with control subjects. In vitro study, significantly altered levels of TXNIP, TRX, MDA, SOD and ROS in HNECs were found following treatment of TXNIP siRNA with or without NAC on HNECs. Conclusion TXNIP expression was increased and TRX expression was decreased in CRSwNP at both protein and mRNA levels. MDA levels were increased and SOD activities were decreased in CRSwNP. TXNIP may have negative association with TRX, and then decrease SOD activities and increase MDA levels, resulting in the upregulation of ROS and oxidative stress in HNECs, which may play a pivotal role in the pathogenesis of CRSwNP. Future studies are expected to further explore the role and mechanism of TXNIP in CRSwNP.

scholarly journals A Global Analysis of Tandem 3′UTRs in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e48997 ◽  
Author(s):  
Peng Tian ◽  
Yu Sun ◽  
Yuxin Li ◽  
Xiang Liu ◽  
Liang Wan ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Global Analysis ◽  
Eosinophilic Chronic Rhinosinusitis

scholarly journals Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

2020 ◽  
Author(s):  
Ming Wang ◽  
Xiangting Bu ◽  
Ge Luan ◽  
Liqing Lin ◽  
Yang Wang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Nasal Polyps ◽  
Acid Metabolism ◽  
Distinct Type ◽  
Arachidonic Acid Metabolism ◽  
Eosinophil Infiltration ◽  
Phenotypic Traits ◽  
Molecular Signatures ◽  
Type 2 Cytokines

Abstract Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP+AS. Methods: A total of 195 subjects; including 65 CRSwNP+AS patients, 99 patients with CRSwNP-alone, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP+AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions: Patients with CRSwNP+AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

scholarly journals Relationships between IL-17A and Macrophages or MUC5AC in Eosinophilic Chronic Rhinosinusitis and Proposed Pathological Significance

2012 ◽  
Vol 3 (2) ◽  
pp. ar.2012.3.0030 ◽  
Author(s):  
Noritsugu Ono ◽  
Takeshi Kusunoki ◽  
Katsuhisa Ikeda
Keyword(s):  
Airway Inflammation ◽  
Chronic Rhinosinusitis ◽  
Neutrophil Elastase ◽  
Nasal Polyps ◽  
Mucus Hypersecretion ◽  
Promotive Factors ◽  
Chemotactic Protein ◽  
Eosinophilic Chronic Rhinosinusitis ◽  
Semithin Sections ◽  
The Mean

Recently, some researchers have reported that macrophages and neutrophils were related to severe asthma. Mucus hypersecretion and persistent airway inflammation result from increased expression of mucin gene (MUC5AC). Eosinophilic chronic rhinosinusitis (ECRS) is considered as intractable rhinosinusitis. From the viewpoint of “one way one disease,” we examined whether ECRS is associated with infiltrating macrophages, neutrophils, their promotive factors, and MUC5AC. We examined 21 nasal polyps with CRS. Each specimen was fixed in 10% phosphate-buffered formalin, embedded in paraffin, processed routinely, and then prepared as semithin sections (3.5 μm). We immunohistochemically observed the macrophages by using CD68, neutrophils by using neutrophil elastase and the promotive factors, monocyte chemotactic protein (MCP) 1, IL-17A, and IL-8, in both ECRS and non-ECRS. The number of macrophages (CD68+ cells), IL-17A, and MUC5AC+ cells in ECRS were significantly greater than in non-ECRS. The mean number of MCP-1+ cells in ECRS was greater than that in non-ECRS, but not significantly. There was a significant correlation in all cases between IL-17A and macrophages or MUC5AC+ cells. Neither the numbers of neutrophils (positive cells for neutrophil elastase) nor the IL-8+ cells showed any significant differences between ECRS and non-ECRS. Our study suggested that infiltrating macrophages, IL-17A and MUC5AC, as well as eosinophils could have roles in the development of ECRS.

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