SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells

Mo, Yuqing; Ye, Ling; Cai, Hui; Zhu, Guiping; Wang, Jian; Zhu, Mengchan; Song, Xixi; Yang, Chengyu; Jin, Meiling

doi:10.1186/s12931-021-01757-1

Cited by 14 publications

(18 citation statements)

References 27 publications

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“…Here, we show for the first time that SERPINB10 expression was significantly increased in induced sputum in asthmatic patients. This is consistent with previously reported increases in asthmatic airway epithelium and lung tissue in HDM/OVA asthmatic mice [16]. Increased SER-PINB10 expression in induced sputum in patients with asthma may be due to secretion of airway epithelial cells or other inflammatory cells, such as lymphocytes or eosinophils.…”

Section: Discussionsupporting

confidence: 93%

“…Down-regulation of SER-PINB10 expression reduces airway hyperresponsiveness and eosinophilic inflammation in a mouse model of asthma. We also found that SERPINB10 may be involved in inhibiting asthma allergic inflammation and Th2 response by inhibiting Th2 cell apoptosis [16]. However, the expression of SERPINB10 protein in induced sputum and its relationship with airway type 2 inflammation in asthma remain unclear.…”

Section: Introductionmentioning

confidence: 81%

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Increased SERPINB10 Expression in Induced Sputum Was Associated with Airway Type 2 Inflammation in Asthma

Zong

Liang

2022

Int Arch Allergy Immunol

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Background: Asthma is a common chronic airway inflammation in the world. The aim of this study was to investigate the expression of SERPINB10 in induced sputum and its correlation with airway type 2 inflammation in asthma. Methods: We recruited 90 subjects and detected SERPINB10 levels in induced sputum by ELISA and analyzed the correlation between SERPINB10 expression levels and FeNO, eosinophils in peripheral blood, lung function, and Th2 cytokines (IL-4, IL-5, and IL-13). Results: The levels of SERPINB10 in induced sputum in asthmatic patients were higher than healthy controls. SERPINB10 levels in induced sputum were positively correlated with FeNO (r = 0.4620, p < 0.0001) and eosinophils in peripheral blood (r = 0.2500, p = 0.0218) and negatively correlated with FEV1 (%predicted) (r = −0.4161, p < 0.0001) and FEV1/FVC% (r = −0.4383, p < 0.0001). SERPINB10 levels were correlated with Th2 cytokines IL-4 (r = 0.6274, p < 0.0001), IL-5 (r = 0.5166, p < 0.0001), and IL-13 (r = 0.5212, p = 0.0003) in asthma. Conclusions: SERPINB10 levels in induced sputum of asthmatic patients were significantly increased and correlated with asthmatic airway type 2 inflammation. Induced sputum SERPINB10 may be a signature protein for type 2 high asthma and may be a potential target for airway eosinophilic inflammation in asthma.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 81%

Increased SERPINB10 Expression in Induced Sputum Was Associated with Airway Type 2 Inflammation in Asthma

Zong

Liang

2022

Int Arch Allergy Immunol

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“…Studies showed that increased levels of SERPINB10 mRNA in epithelial cells of patients with asthma can lead to allergic airway inflammation, which is positively correlated with AHR, sputum eosinophil percentage, and exhaled nitric oxide content ( 50 ). Interestingly, the stimulation of T cell receptor with anti-CD3 antibody can upregulate the expression of SERPINB10 in Th2-polarized cells but has no effect on the expression of SERPINB10 in Th1-polarized cells, proving that it is a stable marker in non-Th2-type asthma ( 51 ). Severe asthma is dominated by Th1/Th17 cytokine responses and rarely has a Th2-mediated immune imbalance ( 52 ), whereas this phenomenon is consistent with our findings.…”

Section: Discussionmentioning

confidence: 99%

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

et al. 2022

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BackgroundAutophagy has been proven to play an important role in the pathogenesis of asthma and the regulation of the airway epithelial immune microenvironment. However, a systematic analysis of the clinical importance of autophagy-related genes (ARGs) regulating the immune microenvironment in patients with asthma remains lacking.MethodsClustering based on the k-means unsupervised clustering method was performed to identify autophagy-related subtypes in asthma. ARG-related diagnostic markers in low-autophagy subtypes were screened, the infiltration of immune cells in the airway epithelium was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. On the basis of the expression of ARGs and combined with asthma control, a risk prediction model was established and verified by experiments.ResultsA total of 66 differentially expressed ARGs and 2 subtypes were identified between mild to moderate and severe asthma. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes, and the low-autophagy subtype was closely associated with severe asthma, energy metabolism, and hormone metabolism. The autophagy gene SERPINB10 was identified as a diagnostic marker and was related to the infiltration of immune cells, such as activated mast cells and neutrophils. Combined with asthma control, a risk prediction model was constructed, the expression of five risk genes was supported by animal experiments, was established for ARGs related to the prediction model.ConclusionAutophagy plays a crucial role in the diversity and complexity of the asthma immune microenvironment and has clinical value in treatment response and prognosis.

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“…Although the mechanisms underlying asthma are unclear, some of these hub genes are under investigation [ 23 – 29 ]. For example, CST1 is a member of the type 2 cystatin (CST) superfamily, which is known to inhibit the proteolytic activities of cysteine proteases.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that ITLN1 is a biomarker associated with disease susceptibility in asthma [ 28 ]. A study on ERPINB10-knockdown mice found that these groups of mice had diminished numbers of Th2 cells and were more susceptible to apoptosis, indicating that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying key genes and functionally enriched pathways in Th2-high asthma by weighted gene co-expression network analysis

Cao

et al. 2022

BMC Med Genomics

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Background Asthma is a chronic lung disease characterized by reversible inflammation of the airways. The imbalance of Th1/Th2 cells plays a significant role in the mechanisms of asthma. The aim of this study was to identify asthma-related key genes and functionally enriched pathways in a Th2-high group by using weighted gene coexpression network analysis (WGCNA). Methods The gene expression profiles of GSE4302, which included 42 asthma patients and 28 controls, were selected from the Gene Expression Omnibus (GEO). A gene network was constructed, and genes were classified into different modules using WGCNA. Gene ontology (GO) was performed to further explore the potential function of the genes in the most related module. In addition, the expression profile and diagnostic capacity (ROC curve) of hub genes of interest were verified by dataset GSE67472. Results In dataset GSE4302, subjects with asthma were divided into Th2-high and Th2-low groups according to the expression of the SERPINB2, POSTN and CLCA1 genes. A weighted gene coexpression network was constructed, and genes were classified into 7 modules. Among them, the red module was most closely associated with Th2-high asthma, which contained 60 genes. These genes were significantly enriched in different biological processes and molecular functions. A total of 8 hub genes (TPSB2, CPA3, ITLN1, CST1, SERPINB10, CEACAM5, CHD26 and P2RY14) were identified, and the expression levels of these genes (except TPSB2) were confirmed in dataset GSE67472. ROC curve analysis validated that the expression of these 8 genes exhibited excellent diagnostic efficiency for Th2-high asthma and Th2-low asthma. Conclusions The study provides a novel perspective on Th2-high asthma by WGCNA, and the hub genes and potential pathways involved may be beneficial for the diagnosis and management of Th2-high asthma.

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SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells

Cited by 14 publications

References 27 publications

Increased SERPINB10 Expression in Induced Sputum Was Associated with Airway Type 2 Inflammation in Asthma

Increased SERPINB10 Expression in Induced Sputum Was Associated with Airway Type 2 Inflammation in Asthma

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

Identifying key genes and functionally enriched pathways in Th2-high asthma by weighted gene co-expression network analysis

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