Regulation and Function of Interferon-Lambda (IFNλ) and Its Receptor in Asthma

Krammer, Susanne; Gutu, Cristina Sicorschi; Grund, Janina C.; Chiriac, Mircea T.; Zirlik, Sabine; Finotto, Susetta

doi:10.3389/fimmu.2021.731807

Cited by 18 publications

(15 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have showed that type-III interferon response was strongly induced by respiratory viruses in nasal epithelial cells [37] highlighting that an impairment of this response might contribute to the defective antiviral response in asthma. However in the context of asthma, major differences were observed between in vivo studies and in vitro studies performed in isolated bronchial epithelial cells: with most in vivo studies showing an antiviral IFNλ induction in asthma, while, similarly to our own results, majority of the in vitro studies report a defect of IFNλ [38]. The current increase of studies on the type-III interferon response to respiratory viruses should unveil in the coming years the potential benefic effect of altering the IFNλ response and impact on patients.…”

Section: Discussionsupporting

confidence: 74%

Airway epithelial response to RSV is impaired in multiciliated and goblet cells in asthma

Gay

Banchero

Carpaij

et al. 2023

Preprint

View full text Add to dashboard Cite

In patients with asthma, respiratory syncytial virus (RSV) infections can cause disease exacerbations by infecting the epithelial layer of the airways, inducing an innate and adaptive immune response. The type-I interferon antiviral response of epithelial cells upon RSV infection is found to be reduced in asthma in most -but not all- studies. Moreover, the molecular mechanisms that cause the differences in the asthmatic bronchial epithelium in response to viral infection are poorly understood. Here, we investigated the transcriptional response to RSV infection of primary bronchial epithelial cells (pBECs) from asthma patients(n=8) and healthy donors(n=8). The pBECs obtained from bronchial brushes were differentiated in air-liquid interface conditions and infected with RSV. After three days, cells were processed for single-cell RNA sequencing. A strong antiviral response to RSV was observed for all cell types present, from both asthma patients and healthy donors. Most differentially regulated genes following RSV infection were found in cells transitioning from basal to secretory. Goblet cells from asthma patients showed lower expression of genes involved in the interferon response. In multiciliated cells, an impairment of the signaling pathways involved in the response to RSV in asthma was observed, including no enrichment of the type-III interferon response. Our results highlight that the response to RSV infection of the bronchial epithelium in asthma and healthy airways was largely similar. However, in asthma, the response of goblet and the multiciliated cells was impaired, highlighting the need for studying airway epithelial cells at high resolution in the context of asthma exacerbations.

show abstract

Section: Discussionsupporting

confidence: 74%

Airway epithelial response to RSV is impaired in multiciliated and goblet cells in asthma

Gay

Banchero

Carpaij

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…TLR7 can induce the expression of IFN- γ , decrease the proportion of Th2 cells, enhance Th1/Treg responses to aeroallergens, and reduce proeosinophil aggregation and chemokine and IgE synthesis [ 78 , 79 ]. The activation of TLR7/8 can enhance IFN λ receptor expression and reduce the airway inflammatory response [ 80 ]. In this study, we measured the levels of IL-4, IL-17, IFN- γ , and IL-10.…”

Section: Discussionmentioning

confidence: 99%

Integrated Network Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Sijunzi Decoction Involved in Alleviating Airway Inflammation in a Mouse Model of Asthma

Jia

Zhao

et al. 2023

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. Asthma is a chronic inflammatory disease of the airways with recurrent attacks, which seriously affects the patients’ quality of life and even threatens their lives. The disease can even threaten the lives of patients. Sijunzi decoction (SJZD), a classical Chinese medicine formula with a long history of administration, is a basic formula used for the treatment of asthma and demonstrates remarkable efficacy. However, the underlying mechanism has not been elucidated. Materials and Methods. We aimed to integrate network pharmacology and intestinal flora sequencing analysis to study the mechanism of SJZD in the treatment of allergic asthmatic mice. The active compounds of SJZD and their asthma-related targets were predicted by various databases. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify potentially relevant pathways for target genes. Furthermore, the active compound-target and target-signaling pathway network maps were constructed by using Cytoscape 3.8.2. These results were combined with those of the intestinal flora sequencing analysis to study the influence of SJZD on airway inflammation in allergic asthmatic mice. Result. We obtained 137 active compounds from SJZD and associated them with 1445 asthma-related targets acquired from the databases. A total of 109 common targets were identified. We visualized active compound-target and target-signaling pathway network maps. The pathological analysis and inflammation score results suggested that SJZD could alleviate airway inflammation in asthmatic mice. Sequencing analysis of intestinal flora showed that SJZD could increase the relevant abundance of beneficial bacterial genus and maintain the balance of the intestinal flora. The core toll-like receptor (TLR) signaling pathway was identified based on network pharmacology analysis, and the important role TLRs play in intestinal flora and organismal immunity was also recognized. The analysis of the correlation between environmental factors and intestinal flora revealed that beneficial bacterial genera were negatively correlated with TLR2 and positively correlated with the TLR7 expression. Furthermore, they were positively correlated with IFN-γ and IL-10 levels and negatively correlated with IL-4 and IL-17 levels. Conclusion. SJZD alleviated the airway inflammation state in asthmatic mice. The findings suggest that increasing the relevant abundance of beneficial intestinal bacteria in mice with asthma, regulating intestinal flora, interfering with the level of TLR2 and TLR7 expression to adjust the secretion of inflammatory factors, and alleviating asthmatic airway inflammation may be the possible mechanism involved in the treatment of asthma by SJZD, providing a basis for further studies on SJZD.

show abstract

“…It is widely accepted that asthma exacerbation after RV infection is in part related to a deficient IFN-response which, in turn, leads to T2-inflammation (Duerr et al, 2016). Nevertheless, many studies, particularly in adult populations, did not observe such a deficient IFN-response, or even found an increased response (Krammer et al, 2021;Yang et al, 2021;Jackson and Gern, 2022;Liew et al, 2022). These inconsistent observations may rely on the baseline level of asthma control and severity between studies, the population age, the model used, and/or the experimental settings.…”

Section: Discussionmentioning

confidence: 99%

Altered cell function and increased replication of rhinoviruses and EV-D68 in airway epithelia of asthma patients

Essaidi-Laziosi

Royston²,

Boda³

et al. 2023

Front. Microbiol.

View full text Add to dashboard Cite

IntroductionRhinovirus (RV) infections constitute one of the main triggers of asthma exacerbations and an important burden in pediatric yard. However, the mechanisms underlying this association remain poorly understood.MethodsIn the present study, we compared infections of in vitro reconstituted airway epithelia originating from asthmatic versus healthy donors with representative strains of RV-A major group and minor groups, RV-C, RV-B, and the respiratory enterovirus EV-D68.ResultsWe found that viral replication was higher in tissues derived from asthmatic donors for all tested viruses. Viral receptor expression was comparable in non-infected tissues from both groups. After infection, ICAM1 and LDLR were upregulated, while CDHR3 was downregulated. Overall, these variations were related to viral replication levels. The presence of the CDHR3 asthma susceptibility allele (rs6967330) was not associated with increased RV-C replication. Regarding the tissue response, a significantly higher interferon (IFN) induction was demonstrated in infected tissues derived from asthmatic donors, which excludes a defect in IFN-response. Unbiased transcriptomic comparison of asthmatic versus control tissues revealed significant modifications, such as alterations of cilia structure and motility, in both infected and non-infected tissues. These observations were supported by a reduced mucociliary clearance and increased mucus secretion in non-infected tissues from asthmatic donors.DiscussionAltogether, we demonstrated an increased permissiveness and susceptibility to RV and respiratory EV infections in HAE derived from asthmatic patients, which was associated with a global alteration in epithelial cell functions. These results unveil the mechanisms underlying the pathogenesis of asthma exacerbation and suggest interesting therapeutic targets.

show abstract

Regulation and Function of Interferon-Lambda (IFNλ) and Its Receptor in Asthma

Cited by 18 publications

References 129 publications

Airway epithelial response to RSV is impaired in multiciliated and goblet cells in asthma

Airway epithelial response to RSV is impaired in multiciliated and goblet cells in asthma

Integrated Network Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Sijunzi Decoction Involved in Alleviating Airway Inflammation in a Mouse Model of Asthma

Altered cell function and increased replication of rhinoviruses and EV-D68 in airway epithelia of asthma patients

Contact Info

Product

Resources

About