Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

Hong, Haiyu; Liao, Shumin; Chen, Fenghong; Yang, Qintai; Wang, De Yun

doi:10.1111/all.14526

Cited by 140 publications

(126 citation statements)

References 105 publications

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“…We propose a concept of “adult‐onset eosinophilic airway diseases” including asthma, N‐ERD, ABPA/ABPM, CRSwNP/eosinophilic CRS, and EGPA. Common pathophysiology such as EETosis/mucus plug formation and common genetic backgrounds including TSLP/IL‐33 pathway genes seem to underlie these diseases 153,154 . In addition, each disease exhibits a specific pathophysiology such as mast cell and platelet activation in N‐ERD, fungal sensitization in ABPA/ABPM, abnormality in coagulation/fibrinolysis pathway in CRSwNP/eosinophilic CRS and autoimmunity in EGPA.…”

Section: Resultsmentioning

confidence: 99%

“…Common pathophysiology such as EETosis/ mucus plug formation and common genetic backgrounds including TSLP/IL-33 pathway genes seem to underlie these diseases. 153,154 In addition, each disease exhibits a specific pathophysiology such as mast cell and platelet activation in N-ERD, fungal sensitization in ABPA/ABPM, abnormality in coagulation/fibrinolysis pathway in CRSwNP/eosinophilic CRS and autoimmunity in EGPA. The clinical efficacy of anti-IL-5 treatments was also variable among the diseases, high for eosinophilic asthma, ABPA/ABPM and EGPA, whereas low for N-ERD and CRSwNP/eosinophilic CRS (Table 1).…”

Section: Con Clus Ionmentioning

confidence: 99%

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Adult‐onset eosinophilic airway diseases

Asano

Ueki

Tamari

et al. 2020

Allergy

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Allergic diseases in the upper and the lower airways such as allergic rhinitis and atopic asthma are usually accompanied by local eosinophilia and sometimes by peripheral blood eosinophilia. Chronic rhinosinusitis with nasal polyps (CRSwNP) and nonatopic asthma are also characterized by local and systemic eosinophilia; however, there are substantial differences in the age of onset and the presence of atopy. Atopic asthma and allergic rhinitis develop during childhood in most cases and mediated by type 1 hypersensitivity reactions to allergen(s), as are other childhood-onset allergic diseases such as food allergies and eczema. Patients often develop these diseases consecutively as an allergic march (Figure 1), suggesting the presence of common genetic backgrounds and pathophysiology. In contrast to childhood-onset disease, adult-onset asthma frequently presents as a nonatopic and eosinophilic condition, 1-6

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Section: Resultsmentioning

confidence: 99%

Section: Con Clus Ionmentioning

confidence: 99%

Adult‐onset eosinophilic airway diseases

Asano

Ueki

Tamari

et al. 2020

Allergy

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“…Because of the difference in smooth muscle and blood sinus between the lower and upper airways, whether remodelling involves in AR is still controversial. Some researches have implied the existence of remodelling in AR [10,11]. Hence, we speculated that refractory AR might be linked to remodelling of the nasal mucosa.…”

Section: Introductionmentioning

confidence: 90%

“…However, whether tissue remodelling of the nasal cavity occurs in AR is uncertain. Nasal remodelling, including goblet cell hyperplasia and collagen deposition, has been reported to occur in AR mice [10,11], whereas other studies have suggested that ani-mal models of AR involve microvascular remodelling of the nasal mucosa [42] and lung remodelling [43]. Additionally, remodelling of the nasal mucosa is reportedly more evident in AR patients with irreversible nasal obstruction [44].…”

Section: Mediators Of Inflammationmentioning

confidence: 99%

The Role of CD40 in Allergic Rhinitis and Airway Remodelling

Cheng

Zhou

Liu

et al. 2021

Mediators of Inflammation

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Background. Allergic rhinitis (AR) affects millions of people and is lack of effective treatment. CD40 is an important costimulatory molecule in immunity. However, few studies have focused on the role of CD40 in AR. Methods. In this study, we built mouse model of chronic AR. The mice were divided into the AR, control, intravenous CD40 siRNA, and nasal CD40 siRNA groups ( n = 6 each). We detected OVA-sIgE, IL-4, IL-5, IL-13, IL-10, IFN-γ, and TGF-β levels in serum and supernatant by ELISA, CD40+ splenic DCs, and Foxp3+ Tregs by flow cytometry and CD40 mRNA by RT2-PCR. We also used PAS and MT stains to assess tissue remodelling. Results. (1) The OVA-sIgE, IL-4, IL-5, and IL-13 levels in the serum or supernatant of nasal septal membrane of AR mice were significantly higher than control. After treated with CD40 siRNA, those indicators were significantly decreased. The IFN-γ, IL-10, and TGF-β levels in AR mice were significantly lower than that in control and were increased by administration of CD40 siRNA. (2) AR mice had significantly fewer Foxp3+ Tregs in the spleen than control mice. After treated with CD40 siRNA, AR mice had significantly more Foxp3+ Tregs. (3) AR mice exhibited a significantly higher CD40 mRNA levels than control. Administration of CD40 siRNA significantly reduced the CD40 mRNA level. (4) The AR mice showed significantly greater collagen deposition than the control in MT staining. Applications of CD40 siRNA significantly reduced the collagen deposition in AR mice. Conclusion. CD40 siRNA therapy shows promise for chronic AR as it significantly attenuated allergic symptoms and Th2-related inflammation and upregulated Foxp3+ Tregs. CD40 plays a role in tissue remodelling in AR, which can be inhibited by CD40 siRNA application.

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“…Furthermore, the level of TSLP expression in patients with asthma is correlated with airway obstruction and disease severity [12] . Moreover, some recent clinical studies using anti-TSLP mAb have yielded promising results [13] . However, these studies mainly employ intraperitoneal or subcutaneous injections, at present, while inhaled medications remain the mainstream approach for clinical asthma treatment, since they are less invasive than injections.…”

Section: Introductionmentioning

confidence: 99%

Transtracheal Instillation of Anti-TSLP Antibody Alleviates Airway Inflammation and Airway Hyperresponsiveness in OVA-Induced Asthma Model Mice

Chen

Fang

Jiang

et al. 2021

Preprint

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BackgroundThymic stromal lymphopoietin (TSLP) is a mainly epithelial cell-derived cytokine that may be important in initiating T2 allergic inflammation. Anti-TSLP antibody inhibit allergic inflammation. Previous animal studies have evaluated the anti-allergic efficacy of injecting anti-TSLP antibody intraperitoneally, subcutaneously, or intravenously. However, transtracheal instillation, a less invasive route for anti-TSLP antibody administration, is hitherto unstudied. This study evaluates the efficacy of transtracheally instilling anti-TSLP antibody in inhibiting airway inflammation and hyperresponsiveness in OVA-induced asthma model Balb/c mice.MethodsBalb/c mice were randomly divided into four groups: the control group, the OVA-induced asthma model group, the anti-TSLP mAb treatment group (TSLP mAb group), and the IgG2a mAb control group (IgG2a mAb group). Each group contained nine to eleven mice. Mice in the asthma model group were sensitized with OVA to trigger allergic responses and were treated with transtracheal instillation of normal saline. Mice in the TSLP mAb group received transtracheal instillation of anti-TSLP mAb, while mice in the IgG2a group received transtracheal instillation of IgG2a mAb. Both of these groups were then subjected to OVA challenge. Airway responsiveness was measured as an enhanced pause (Penh) using noninvasive plethysmography. The severity of inflammation was evaluated by histopathological examination using the Underwood assessment of the lung sections. Changes in expression of TSLP, TSLP receptor (TSLPR), T-box transcription factor (T-bet), GATA binding protein 3 (GATA3) and forkhead box protein P3 (Foxp3) were assessed using RT-PCR and immunohistochemical staining. ResultsAirway hyperresponsiveness and infiltration of airway inflammatory cells in the TSLP mAb group were significantly reduced, compared with the OVA and the IgG2a mAb groups. Meanwhile，TSLP, GATA3 mRNA expression and GATA3 protein levels were significantly decreased in the TSLP mAb group, compared with the OVA and the IgG2a mAb groups (P＜0.05）. No significant differences were observed in either T-bet or Foxp3 in the lung section of mRNA and protein expression among these four groups (P＞0.05).ConclusionTranstracheal instillation of anti-TSLP antibody attenuated lung inflammation and airway hyperresponsiveness in OVA-induced asthmatic mice, possibly through downregulation of perivascular and peribronchiolar lymphocytes, neutrophils and GATA3 expression in the airway.

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Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

Cited by 140 publications

References 105 publications

Adult‐onset eosinophilic airway diseases

Adult‐onset eosinophilic airway diseases

The Role of CD40 in Allergic Rhinitis and Airway Remodelling

Transtracheal Instillation of Anti-TSLP Antibody Alleviates Airway Inflammation and Airway Hyperresponsiveness in OVA-Induced Asthma Model Mice

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