Nasal Epithelial Barrier Integrity and Tight Junctions Disruption in Allergic Rhinitis: Overview and Pathogenic Insights

Husna, Siti Muhamad Nur; Tan, Hern‐Tze Tina; Shukri, Norasnieda Md; Ashari, Noor Suryani Mohd; Wong, Kah Keng

doi:10.3389/fimmu.2021.663626

Cited by 57 publications

(50 citation statements)

References 131 publications

(176 reference statements)

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“…Six of the seven TJ genes ( CLDN4 , CLDN6 , CLDN7 , CLDN12 , TJP1 , and TJP2 ), which demonstrated negative association with both IL4R and IL13RA1 expression levels, have been implicated in AR such as significantly decreased expression in nasal epithelium of AR patients compared with non-allergic controls ( Brandner, 2016 ; Siti Sarah et al, 2020 ; Nur Husna et al, 2021a ). Moreover, our correlation analysis observation corroborates with the increased expression of Tjp2 , Cldn7, and Cldn15 in epithelial cells of Stat6 −/− mice ( Lin et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Allergic rhinitis (AR) is a common chronic inflammatory disease with high prevalence across different regions of the globe ( Greiner et al, 2011 ; Pawankar, 2014 ; Sani et al, 2019 ; Tan et al, 2020 ). AR is characterized by aberrantly high Th2 cytokines levels such as interleukin-4 (IL-4), IL-5, IL-6, and IL-13 ( Nur Husna et al, 2021a ). IL-4 and IL-13 are key pathogenic Th2 cytokines in AR where they activate B cells to synthesize IgE, induce goblet cell hyperplasia, trigger airway hyperresponsiveness, and mucus hypersecretion ( Wills-Karp and Finkelman, 2008 ; Sahoo et al, 2016 ; Bezerra Barros et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Multiple studies have indicated the disruption of nasal epithelial barrier as the underlying cause of AR ( Takano et al, 2005 ; Steelant et al, 2018 ; Nur Husna et al, 2021a ). It has been proposed that Th2 cytokines signal through their respective receptors on nasal epithelial cells to suppress expression of TJs ( Steelant et al, 2018 ; Nur Husna et al, 2021a ). However, there is a lack of literature on the expression of interleukin receptors in nasal epithelial cells of AR patients.…”

Section: Introductionmentioning

confidence: 99%

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IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

Husna

Shukri

Sharif

et al. 2022

Front. Mol. Biosci.

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The IL-4/IL-13 axis is involved in the pathogenesis of allergic rhinitis (AR). In this study, we investigated the serum cytokines levels of IL-4, IL-5, IL-6, and IL-13 in AR patients, and the transcript expression levels of their receptors (i.e. IL4R, IL5RA, IL6R, and IL13RA1) in nasal epithelial cells of AR patients versus non-allergic controls. Nasal epithelial cells and blood samples of non-allergic controls (n = 30) and AR patients (n = 30) were collected to examine mRNA expression and serum cytokines levels, respectively. Bioinformatics analyses of IL-4/IL-13 receptor heterodimer association with tight junction (TJ) and JAK/STAT signaling genes were conducted in a gene expression profiling (GEP) dataset (GSE44037) of AR patients (n = 12) and healthy controls (n = 6). Serum IL-4, IL-5, IL-6 or IL-13 levels, and IL13RA1 transcript expression were significantly higher in AR patients compared with non-allergic controls. IL-4 and IL-13 serum levels were positively correlated with IL13RA1 expression in AR patients but not in non-allergic controls. In the GEP dataset (GSE44037), six TJ (CLDN4, CLDN7, CLDN12, CLDN15, TJP1, and TJP2) genes’ expressions were negatively correlated, respectively, with IL-4Rα/IL-13Rα1 heterodimeric receptor expression in AR patients and not in control samples. These six TJ genes contributed to the significant enrichment of tight junction Gene Ontology (GO ID: 0070160). Lastly, STATs DNA binding motif analysis showed that each of these TJ genes contains STATs binding consensus sequence within intronic and intergenic regions. Our results suggest that increased IL-4/IL-13 serum cytokines levels may contribute to decreased TJs expression via IL-4Rα/IL-13Rα1 heterodimeric receptor in nasal epithelium of AR patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

Husna

Shukri

Sharif

et al. 2022

Front. Mol. Biosci.

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“…22 Hence, we hypothesized was attenuated. 32 Hence, the decrement of lnc-PVT1 from W0 to W4 was positively correlated with the decline of TNSS from W0 to W4 in AR children.…”

Section: Discussionmentioning

confidence: 83%

Aberrant expression of long non‐coding RNA PVT1 in allergic rhinitis children: Correlation with disease risk, symptoms, and Th1/Th2 imbalance

Sun¹,

Han

Ma³

et al. 2022

Clinical Laboratory Analysis

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Background: Long non-coding RNA plasmacytoma variant translocation 1 (lnc-PVT1) exacerbates inflammation and induces T helper (Th) 1/Th2 imbalance in allergic diseases, but its clinical role in allergic rhinitis (AR) remains unclear. Hence, we conducted this study to compare lnc-PVT1 expression among AR children, disease controls (DCs), and health controls (HCs), aiming to investigate its clinical application in AR children.Methods: Sixty AR children, 30 DCs, and 30 HCs were enrolled in the study, and then, their lnc-PVT1 expression in peripheral blood mononuclear cell was detected.Serum interferon-gamma (IFNγ), interleukin 10 (IL-10), Th1, and Th2 cells in AR children were also analyzed. Besides, lnc-PVT1 was also detected at Week (W)4 after treatment in AR patients. Results: Lnc-PVT1 was upregulated in AR children compared with DCs and HCs (both p < 0.001). Lnc-PVT1 was positively related to nasal rhinorrhea score, itching score, congestion score, and total nasal symptom score (TNSS) in AR children (all p < 0.050), instead of sneezing score (p = 0.115). Lnc-PVT1 negatively associated with Th1 cells in AR children (p = 0.028) also exhibited a negative correlation trend with IFNγ (but without statistical significance) (p = 0.065). Differently, lnc-PVT1 was positively related to Th2 cells (p = 0.012) and IL-10 (p = 0.021) in AR children. Besides, lnc-PVT1 and TNSS were reduced at W4 after treatment in AR children (both p < 0.001); notably, lnc-PVT1 expression decline was correlated with TNSS decline during treatment (p = 0.013). Conclusion:Lnc-PVT1 works as a biomarker, whose aberrant expression is related to disease severity, Th1/Th2 imbalance, and its decrement can reflect treatment outcome in AR children.

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“…Therefore, it is essential to determine the individual's allergen sensitization for the diagnosis and treatment of allergies (14). Characteristics such as environmental factors (e.g., geographical area) and demographic factors (e.g., age and sex) influence the pattern of inhalant allergen (including HDM) sensitization (15)(16)(17)(18)(19). The degree of sensitivity of a patient toward allergens is ascertained by the size of the wheal formed during SPT (20).…”

Section: Introductionmentioning

confidence: 99%

Higher Wheal Sizes of Dermatophagoides farinae Sensitization Exhibit Worse Nasal Symptoms in Allergic Rhinitis Patients

et al. 2022

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Allergic rhinitis (AR) is a global health burden and it manifests in both nasal and non-nasal symptoms. Skin prick test (SPT) is a routine procedure to diagnose AR sensitized to common allergens including house dust mites (HDMs). The degree of sensitivity of a patient toward allergens is determined by the size of the wheal formed by SPT procedure. SPT wheal sizes are influenced by recent anti-histamine usage, however it remains unclear if SPT wheal sizes are also influenced by other factors. In this study, we set out to investigate the association between SPT wheal sizes with the demographical, clinical and environmental characteristics, as well as nasal and non-nasal symptoms severity scores, of AR patients (n = 30) sensitized to common HDMs (i.e., Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis). We showed that SPT wheal sizes of HDM allergens were not associated with clinical, demographical and environmental characteristics examined. Nonetheless, significant correlations were observed between SPT wheal sizes of D. farinae sensitization with worse severity scores of all five nasal symptoms examined (i.e., sneezing, runny nose, itchy nose, congestion and postnasal drip) and four of the six non-nasal symptoms examined (i.e., throat symptoms, ear symptoms, headache and mental function). Such relationships were not observed in SPT wheal sizes of D. pteronyssinus and B. tropicalis sensitization. We suggest that increased SPT wheal sizes for D. farinae sensitization may predict the likelihood of more severe nasal and, to a lesser extent, non-nasal manifestations in AR patients.

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Nasal Epithelial Barrier Integrity and Tight Junctions Disruption in Allergic Rhinitis: Overview and Pathogenic Insights

Cited by 57 publications

References 131 publications

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

Aberrant expression of long non‐coding RNA PVT1 in allergic rhinitis children: Correlation with disease risk, symptoms, and Th1/Th2 imbalance

Higher Wheal Sizes of Dermatophagoides farinae Sensitization Exhibit Worse Nasal Symptoms in Allergic Rhinitis Patients

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