Pathogenesis Of Asthma Research Articles

STC-1 alleviates airway inflammation by regulating epithelial cell apoptosis through the 5-LO pathway.

Airway inflammation plays a key role in the pathogenesis and development of asthma. Stanniocalcin-1 (STC-1) has powerful antioxidant, anti-inflammatory and anti-apoptotic functions but its impact on the airway inflammation in asthma lacks evidence. Here, we investigated the effect and potential mechanism of STC-1 on airway inflammation through asthmatic mice model and lipopolysaccharide (LPS)-treated BEAS-2B cells. The data showed that STC-1 treatment before the challenge exerted protective effect on ovalbumin (OVA)-induced asthmatic mice, i.e., decreased the inflammatory cell infiltration, mucus secretion, cytokine levels, apoptosis levels, and p38 MAPK signaling. Additionally, STC-1 reduced 5-LO expression. Meanwhile, STC-1 decreased p38 MAPK signaling, cytokine production, mucin MUC5AC production, 5-LO expression and nuclear translocation, and LTB4 production in vitro. Ultimately, transforming growth factor (TGF- ), as a 5-LO inducer, reversed the anti-inflammatory and anti-apoptotic effects of STC-1 in BEAS-2B cells by up-regulating 5-LO expression. It reveals the potential of STC-1 to act as an additional therapy to mitigate airway inflammation in asthma and inhibit 5-LO expression.

Integrating nontargeted metabolomics and RNA sequencing of dexamethasone-treated and untreated asthmatic mice reveals changes of amino acids and aminoacyl-tRNA in group 2 innate lymphoid cells.

Bronchial asthma is the most common multifactorial and heterogeneous disease in childhood. The glucocorticoid dexamethasone is a classic treatment for asthma. Research indicates that group 2 innate lymphoid cells (ILC2s) are crucial to the pathogenesis of asthma. However, few studies have focused on ILC2s metabolism and transcription. This study aims to establish an ovalbumin (OVA)-induced asthma model and a dexamethasone-treated asthma model to explore the regulation of lung ILC2s at the genetic and metabolic levels during the progression and remission of asthma, utilizing single-cell metabolomics and transcriptomics approaches. The results showed that ILC2s regulated the metabolic pathways and transcriptional levels of amino acids (such as arginine, proline, and histidine) and linoleic acid, as well as the metabolic biomarkers of arginine, urocanic acid, and linoleic acid in asthma. Additionally, the cytokine pathways and NF-γB pathways have been altered at the genetic level. At the same time, we revealed that dexamethasone regulates ILC2s amino acid and aminoacyl tRNA metabolism, as well as related genes, thereby alleviating asthma symptoms. Furthermore, we identified the genes Eno3 and Tap1, which are significantly associated with asthma. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the accuracy of the RNA sequencing results. This study, for the first time, revealed the mechanistic changes of ILC2s in the development and treatment of asthma using multiomics techniques, laying a foundation for targeted therapies in asthma.

DEPTOR attenuates asthma progression by suppressing endoplasmic reticulum stress through SOD1.

Endoplasmic reticulum (ER) stress has been shown to play a pivotal role in the pathogenesis of asthma. DEPTOR (DEP Domain Containing MTOR Interacting Protein) is an endogenous mTOR inhibitor that participates in various physiological processes such as cell growth, apoptosis, autophagy, and ER homeostasis. However, the role of DEPTOR in the pathogenesis of asthma is still unknown. In this study, an ovalbumin (OVA)-induced mice model and IL-13 induced 16HBE cells were used to evaluate the effect of DEPTOR on asthma. A decreased DEPTOR expression was shown in the lung tissues of OVA-mice and IL-13 induced 16HBE cells. Upregulation of DEPTOR attenuated airway goblet cell hyperplasia, inhibited mucus hypersecretion, decreased the expression of mucin MUC5AC, and suppressed the level of inflammatory factors IL-4 and IL-5, which were all induced by OVA treatment. The increased protein expression of ER stress markers GRP78, CHOP, unfolded protein response (UPR) related proteins, and apoptosis markers in OVA mice were also inhibited by DEPTOR overexpression. In IL-13 induced 16HBE cells, overexpression of DEPTOR decreased IL-4, IL-5, and MUC5AC levels, preventing ER stress response and UPR process. Furthermore, from the proteomics results, we identified that SOD1 (Cu/Zn Superoxide Dismutase 1) may be the downstream factor of DEPTOR. Similar to DEPTOR, upregulation of SOD1 alleviated asthma progression. Rescue experiments showed that SOD1 inhibition abrogates the remission effect of DEPTOR on ER stress in vitro. In conclusion, these data suggested that DEPTOR attenuates asthma progression by suppressing endoplasmic reticulum stress through SOD1.

Identification of TXN and F5 as novel diagnostic gene biomarkers of the severe asthma based on bioinformatics and machine learning analysis

Asthma poses a major threat to human health. The aim of this study was to identify genetic markers of severe asthma and analyze the relationship between key genes and immune infiltration. Differentially expressed genes (DEGs) were first screened by downloading the training set GSE69683 and validation set GSE137268 from the GEO dataset. SVM-RFE analysis and the LASSO regression model were used to screen key genes, and CIBERSORT was used to assess immune infiltration in the samples. A total of 20 DEGs were identified in this study, mainly enriched for lymph node-like receptors, b-cell receptors, and neutrophil extracellular trap pathway. Comparative validation set GSE137268 identified thioredoxin (TXN) and coagulation factor V (F5) were identified as diagnostic markers of severe asthma. CIBERSORT analysis revealed that TXN and F5 are associated with multiple immune cell infiltrates. In addition, we identified miRNA and TF at the transcriptional level that may regulate F5 and TXN, and found that several commonly used drugs may exert therapeutic effects by targeting F5 and TXN. Taken together, TXN and F5 may be key genes in the development of severe asthma and are associated with immune infiltration. Our study can help to better understand the pathogenesis of asthma and provide new ideas for clinical treatment.

Effect of Tezepelumab on Sino-Nasal Outcome Test (SNOT)-22 Domain and Symptom-Specific Scores in Patients with Severe, Uncontrolled Asthma and a History of Chronic Rhinosinusitis with Nasal Polyps.

Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes. Patients (aged 12-80years) with severe, uncontrolled asthma were randomized to tezepelumab 210mg or placebo subcutaneously every 4weeks for 52weeks. SNOT-22 total, domain, and item scores were assessed in patients with a history of CRSwNP. Annualized asthma exacerbation rate (primary efficacy outcome), pre-bronchodilator forced expiratory volume in 1s, and Asthma Control Questionnaire-6, Asthma Quality of Life Questionnaire (standardized) for patients 12years and older, and Asthma Symptom Diary scores were also assessed in patients with and without a history of CRSwNP. Of 1059 patients with severe asthma, 165 (15.6%) had a history of CRSwNP. Tezepelumab treatment resulted in sustained improvements versus placebo in SNOT-22 total score throughout the 52-week study period [least-squares mean difference (95% confidence interval) - 11.08 (- 17.80, - 4.35)]. Tezepelumab improved all five SNOT-22 domain scores (sleep, nasal, function, ear/facial, and emotion) and the five SNOT-22 item scores of most clinical interest (decreased sense of smell/taste, nasal blockage, reduced productivity, waking up tired, and cough). Tezepelumab improved asthma-related clinical outcomes in patients with and without a history of CRSwNP. In patients with severe, uncontrolled asthma and a history of CRSwNP, tezepelumab improved rhinosinusitis symptoms across multiple domains, as well as asthma exacerbations, lung function, asthma control, and health-related quality of life. NCT03347279 ( https://classic. gov/ct2/show/NCT03347279 ).

Unraveling heterogeneity and treatment of asthma through integrating multi-omics data

Asthma has become one of the most serious chronic respiratory diseases threatening people's lives worldwide. The pathogenesis of asthma is complex and driven by numerous cells and their interactions, which contribute to its genetic and phenotypic heterogeneity. The clinical characteristic is insufficient for the precision of patient classification and therapies; thus, a combination of the functional or pathophysiological mechanism and clinical phenotype proposes a new concept called “asthma endophenotype” representing various patient subtypes defined by distinct pathophysiological mechanisms. High-throughput omics approaches including genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome enable us to investigate the pathogenetic heterogeneity of diverse endophenotypes and the underlying mechanisms from different angles. In this review, we provide a comprehensive overview of the roles of diverse cell types in the pathophysiology and heterogeneity of asthma and present a current perspective on their contribution into the bidirectional interaction between airway inflammation and airway remodeling. We next discussed how integrated analysis of multi-omics data via machine learning can systematically characterize the molecular and biological profiles of genetic heterogeneity of asthma phenotype. The current application of multi-omics approaches on patient stratification and therapies will be described. Integrating multi-omics and clinical data will provide more insights into the key pathogenic mechanism in asthma heterogeneity and reshape the strategies for asthma management and treatment.

Exploring potential therapeutic targets for asthma: a proteome-wide Mendelian randomization analysis

BackgroundAsthma poses a significant global health challenge, characterized by high rates of morbidity and mortality. Despite available treatments, many severe asthma patients remain poorly managed, highlighting the need for novel therapeutic strategies. This study aims to identify potential drug targets for asthma by examining the influence of circulating plasma proteins on asthma risk.MethodsThis study employs summary-data-based Mendelian randomization (MR) and two-sample MR methods to investigate the association between 2940 plasma proteins from the UK Biobank study and asthma. The analysis includes discovery (FinnGen cohort) and replication (GERA cohort) phases, with Bayesian colocalization used to validate the relationships between proteins and asthma. Furthermore, protein–protein interaction and druggability assessments were conducted on high-evidence strength protein biomarkers, and candidate drug prediction and molecular docking were performed for proteins without targeted drugs. Given the complexity of asthma pathogenesis, the study also explores the relationships between plasma proteins and asthma-related endpoints (e.g., obesity-related asthma, infection-related asthma, childhood asthma) to identify potential therapeutic targets for different subtypes.ResultsIn the discovery cohort, 75 plasma proteins were associated with asthma, including IL1RAP, IL1RL1, IL6, CXCL5, and CXCL8. Additionally, 6 proteins (IL4R, LTB, CASP8, MAX, PCDH12, and SCLY) were validated through co-localization analysis and validation cohort. The assessment of drug targetability revealed potential drug targets for IL4R, CASP8, and SCLY, while candidate drugs were predicted for LTB and MAX proteins. MAX exhibited strong binding affinity with multiple small molecules indicating a highly stable interaction and significant druggability potential. Analysis of the 75 proteins with 9 asthma-related endpoints highlighted promising targets such as DOK2, ITGAM, CA1, BTN2A1, and GZMB.ConclusionThese findings elucidate the link between asthma, its related endpoints, and plasma proteins, advancing our understanding of molecular pathogenesis and treatment strategies. The discovery of potential therapeutic targets offers new insights into asthma drug target research.

The role of DC subgroups in the pathogenesis of asthma.

Dendritic cells (DCs), specialized antigen-presenting cells of the immune system, act as immunomodulators in diseases of the immune system, including asthma. The understanding of DC biology has evolved over the years to include multiple subsets of DCs with distinct functions in the initiation and maintenance of asthma. Moreover, most strategies for treating asthma with relevant therapeutic agents that target DCs have been initiated from the study of DC function. We discussed the pathogenesis of asthma (including T2-high and T2-low), the roles played by different DC subpopulations in the pathogenesis of asthma, and the therapeutic strategies centered around DCs. This study will provide a scientific theoretical basis for current asthma treatment, provide theoretical guidance and research ideas for developing and studying therapeutic drugs targeting DC, and provide more therapeutic options for the patient population with poorly controlled asthma symptoms.

IRF3 Promotes Asthma Pathogenesis by Regulating Type 2 Innate Lymphoid Cells

ABSTRACT Background Allergic asthma is characterized by airway hyperresponsiveness triggered by inhaled allergens. Type 2 innate lymphoid cells (ILC2s) have been demonstrated to play a crucial role in promoting airway inflammation through the secretion of type 2 effector cytokines. However, the mechanisms underlying the functions of lung ILC2s remain unclear. Methods In this study, we investigated the expression of IRF3 in ILC2s in both human patients and mouse models of asthma. We utilized IRF3-deficient mice to assess the impact of IRF3 deficiency on ILC2 function in a model of IL33-induced asthma. Additionally, we explored the mechanisms underlying IRF3-mediated regulation of ILC2s, focusing on the involvement of the transcription factor Gata3. Results Our findings revealed elevated expression of IRF3 in ILC2s of patients and mice with asthma, suggesting a potential role for IRF3 in the pathogenesis of allergic asthma. Furthermore, we demonstrated that IRF3 deficiency impairedthe expansion and function of ILC2s in IL33-induced asthma, highlighting the importance of IRF3 in regulating ILC2-mediated responses. Importantly, we showed that the regulation of ILC2s by IRF3 was independent of Th2 cells and mediated by the transcription factor Gata3. Conclusion This study identifies IRF3 as a novel regulator of lung ILC2s and suggests its potential as a promising immunotherapeutic target for allergic asthma. These findings shed light on the intricate mechanisms underlying asthma pathogenesis and provide insights into potential strategies for the development of targeted therapies for this prevalent airway disease.

TRIM7 knockdown protects against LPS-induced autophagy, ferroptosis, and inflammatory responses in human bronchial epithelial cells.

Asthma is one of the most common respiratory diseases in pediatric department. Several asthma-associated events including inflammatory responses, autophagy, and ferroptosis have been identified as typical pathological processes. TRIM7 is a member of TRIM proteins family associated with several types of diseases. Nevertheless, its role in asthma is still elusive. The current research showed that TRIM7 was involved in the pathogenesis of asthma mainly by regulating the Akt signaling pathway. In detail, we found that TRIM7 was highly expressed in patients with asthma and in an in vitro model of asthma. The following analysis indicated that TRIM7 knockdown attenuated the expression and secretion of inflammatory cytokines including TNF-α, IL-1β and IL-6 in lipopolysaccharide (LPS)-exposed human bronchial epithelial cells (HBECs). Meanwhile, knockdown of TRIM7 exerted inhibitory effects on LPS-induced autophagy and ferroptosis. Further mechanistic studies showed that TRIM7 knockdown inhibited LPS-induced activation of Akt pathway, while overexpression of Akt attenuated the inhibitory effects of TRIM7 knockdown on LPS-exposed HBECs. Collectively, we reported here that TRIM7 knockdown inhibited LPS-induced autophagy, ferroptosis, and inflammatory cytokine secretion in HBECs via regulating the Akt pathway, providing a new insight into the strategies for improving asthma treatments.

Aging, brain-derived neurotrophic factor, and allergen-induced pulmonary responses in mice.

Asthma in the elderly is being recognized as more severe, resistant to standard therapies, and having greater morbidity. Therefore, it comes important to understand the impact of aging-associated airway structure and function changes towards pathogenesis of asthma in the elderly. Here, airway smooth muscle plays important roles in airway hyperreactivity and structural remodeling. The role of smooth muscle in asthma can be modulated by growth factors (including neurotrophins such as brain-derived neurotrophic factor (BDNF)) and pro-inflammatory senescence factors. In this study, we investigated aging effects on airway hyperreactivity, structural remodeling, inflammation, and senescence in a mouse model of allergic asthma. C57BL/6J wildtype mice or smooth muscle-specific BDNF knockout mice at 4, 18 and 24 months of age were intranasally exposed to mixed allergens (ovalbumin, aspergillus, Alternaria, and house dust mite) over 4 weeks. Assessing lung function by FlexiVent, we found that compared with 4 month old mice, 18 and 24 month old C57BL/6J mice showed decreased airway resistance and increased airway compliance after PBS or MA treatment. Deletion of smooth muscle BDNF blunted airway hyperreactivity in aged mice. Lung histology analysis revealed that aging increased bronchial airway thickness and decreased lung inflammation. Multiplex assays showed that aging largely reduced allergen-induced lung expression of proinflammatory chemokines and cytokines. By immunohistochemistry staining, we found that aging increased bronchial airway expression of senescence markers, including p21, phospho-p53 and phospho-gH2A.X. Our data suggest that aging associated increase of airway senescence in the context of allergen exposure may contribute to asthma pathology in the elderly.

Increased expression of Cathepsin C in airway epithelia exacerbates airway remodeling in asthma.

Airway remodeling is a critical factor determining the pathogenesis and treatment sensitivity of severe asthma (SA) or uncontrolled asthma (UA). The activation of epithelial-mesenchymal trophic units (EMTUs) regulated by airway epithelial cells (AECs) has been proven to induce airway remodeling directly. However, the triggers for EMTU activation and the underlying mechanism of airway remodeling are not fully elucidated. Here, we screened the differentially expressed gene Cathepsin C (CTSC)/dipeptidyl peptidase 1 (DPP-1) in epithelia of SA and UA patients using RNA sequencing data and further verified the increased expression of CTSC in induced sputum of asthma patients which was positively correlated with the severity and airway remodeling. Moreover, direct instillation of exogenous CTSC induced airway remodeling. Genetic inhibition of CTSC suppressed EMTU activation and airway remodeling in two asthma models with airway remodeling. Mechanistically, increased secretion of CTSC from AECs induced EMTU activation through p38-mediated pathway, further inducing airway remodeling. Meanwhile, inhibition of CTSC also reduced the infiltration of inflammatory cells and the production of inflammatory factors in the lungs of asthmatic mice. Consequently, targeting CTSC with compound AZD7986 protected against airway inflammation, EMTU activation and remodeling in asthma model. Based on the dual effects of CTSC on airway inflammation and remodeling, CTSC is a potential biomarker and therapeutic target for SA or UA.

Role of Thymic Stromal Lymphopoietin in the Pathophysiology of Asthma and Clinical and Biological Effects of Blockade With Tezepelumab.

The airway epithelium is the first line of defense of the respiratory system against the external environment. It plays an active role in the initiation of immune and allergic responses against potential hazards. Among the various specialized cells and cytokines that participate in epithelium-induced responses, alarmins are particularly interesting, given their ample role in mediating T2 and non-T2 inflammatory mechanisms involved in the pathogenesis of asthma. Thymic stromal lymphopoietin (TSLP) is an alarmin with broad effects in asthma that result from its widespread action on multiple cell types, including eosinophils, mast cells, dendritic cells, and group-2 innate lymphoid cells. Its role in allergy-mediated responses, eosinophilic inflammation, airway hyperresponsiveness, mucus hyperproduction, viral tolerance, and airway remodeling is of the utmost importance, as more comprehensive asthma assessments have been developed to explore these pathogenic features. Therefore, blockade with targeting molecules, such as monoclonal antibodies, has emerged as a promising therapeutic option, particularly in patients with multiple pathogenic pathways. In this review, we examine the roles of alarmins (mainly TSLP) in the pathogenesis of asthma and clinical expression and discuss the effects of inhibiting TSLP on several inflammatory and clinical outcomes. We also review the literature supporting treatment with anti-TSLP biologics and the unanswered questions and unmet needs associated with targeting alarmins in asthma.

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity.

Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma. We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model. Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues. These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

Use of Targeted Biologic Therapies in Asthma: Current Practice in India

Asthma remains a significant public health issue in India, with a growing number of patients experiencing severe and uncontrolled forms of the disease. Targeted biologic therapies, including omalizumab, mepolizumab, benralizumab, reslizumab, and dupilumab, have emerged as advanced treatment options for patients with severe asthma, especially those with allergic or eosinophilic phenotypes. These therapies work by targeting specific immunological pathways involved in asthma pathogenesis, offering better symptom control and reducing exacerbation rates. However, the high cost of biologics, limited access, and inconsistent insurance coverage pose significant barriers to their widespread use in India. Despite these challenges, real-world data from Indian studies demonstrate promising clinical outcomes with biologic therapies in patients with difficult-to-treat asthma. This review examines the current landscape of biologic use in India, challenges related to cost and accessibility, and future prospects for integrating these treatments into routine asthma care, particularly through cost- reduction strategies and expanded healthcare coverage.

Innate players in Th2 and non-Th2 asthma: emerging roles for the epithelial cell, mast cell, and monocyte/macrophage network.

Asthma is one of the most common chronic respiratory diseases and is characterized by airway inflammation, increased mucus production, and structural changes in the airways. Recently, there is increasing evidence that the disease is much more heterogeneous than expected, with several distinct asthma endotypes. Based on the specificity of T cells as the best-known driving force in airway inflammation, bronchial asthma is categorized into T helper cell 2 (Th2) and non-Th2 asthma. The most studied effector cells in Th2 asthma include T cells and eosinophils. In contrast to Th2 asthma, much less is known about the pathophysiology of non-Th2 asthma, which is often associated with treatment resistance. Besides T cells, the interaction of myeloid cells such as monocytes/macrophages and mast cells with the airway epithelium significantly contributes to the pathogenesis of asthma. However, the underlying molecular regulation and particularly the specific relevance of this cellular network in certain asthma endotypes remain to be understood. In this review, we summarize recent findings on the regulation of and complex interplay between epithelial cells and the "nonclassical" innate effector cells mast cells and monocytes/macrophages in Th2 and non-Th2 asthma with the ultimate goal of providing the rationale for future research into targeted therapy regimens.

Regulation of Airway Epithelial-Derived Alarmins in Asthma: Perspectives for Therapeutic Targets.

Asthma is a chronic respiratory condition predominantly driven by a type 2 immune response. Epithelial-derived alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 orchestrate the activation of downstream Th2 cells and group 2 innate lymphoid cells (ILC2s), along with other immune effector cells. While these alarmins are produced in response to inhaled triggers, such as allergens, respiratory pathogens or particulate matter, disproportionate alarmin production by airway epithelial cells can lead to asthma exacerbations. With alarmins produced upstream of the type 2 inflammatory cascade, understanding the pathways by which these alarmins are regulated and expressed is critical to further explore new therapeutics for the treatment of asthmatic patients. This review emphasizes the critical role of airway epithelium and epithelial-derived alarmins in asthma pathogenesis and highlights the potential of targeting alarmins as a promising therapeutic to improve outcomes for asthma patients.

Traditional Chinese medicine to improve immune imbalance of asthma: focus on the adjustment of gut microbiota.

Asthma, being the prevailing respiratory ailment globally, remains enigmatic in terms of its pathogenesis. In recent times, the advancement of traditional Chinese medicine pertaining to the intestinal microbiota has yielded a plethora of investigations, which have substantiated the potential of traditional Chinese medicine in disease prevention and treatment through modulation of the intestinal microbiota. Both animal models and clinical trials have unequivocally demonstrated the indispensable role of the intestinal microbiota in the pathogenesis of asthma. This article presents a summary of the therapeutic effects of traditional Chinese medicine in the context of regulating gut microbiota and its metabolites, thereby achieving immune regulation and inhibiting airway inflammation associated with asthma. It elucidates the mechanism by which traditional Chinese medicine modulates the gut microbiota to enhance asthma management, offering a scientific foundation for the utilization of traditional Chinese medicine in the treatment of asthma.

Characterisation of C-C Ligand 7 (CCL7) as Asthma Genetic Marker in Pigtailed Monkey.

The pigtailed monkey (Macaca nemestrina) is one of the species that have potency like the cynomolgus monkey that is widely used as an animal model for asthma study. The CCL7 gene has potential as a genetic marker because of the secreted chemokine that plays a role in asthma. The aims of this research are to characterise the CCL7 gene of pigtailed monkey, compare the structure of their CCL7 gene with other primate species and determine model 3D structure protein prediction of CCL7 protein. The amplicons were sequenced, and the results were analysed by the bioinformatics technique. The 3D CCL7 protein structure was predicted using I-TASSER. We have isolated 2221 bp sequences CCL7 gene and 109 amino acids from pigtailed monkey. Variation of CCL7 gene sequence between pigtailed monkey and other primate species (Macaca fascicularis, M. mulatta and Homo sapiens) was found in exon 1, exon 2 and exon 3 as CDS (Coding DNA Sequence) region. The analysis homology of nucleotides and amino acid sequences of the CCL7 gene indicated that the pigtailed monkey and three other primate species have a high homology rate with an identity score above 90%. Meanwhile, a comparative analysis of CDS and amino acid regions showed that the pigtailed monkey also has the highest similarity with the three other primate species with more than 90% identity score. The 3D structure protein prediction model of the CCL7 pigtailed monkey revealed the highest similarity with H. sapiens with an identity value of about 95%. Therefore, the pigtailed monkey CCL7 gene has high similarity with H. sapiens, which means that based on molecular similarity, the pigtailed monkey has the potential to be an animal model for asthma study, especially the study of molecular and the role of CCL7 in asthma pathogenesis.

NFATc1 in CD4+ T cells and CD11c+ dendritic cells drives TH2-mediated eosinophilic inflammation in allergic asthma

BackgroundAsthma, a chronic lung disease, is a significant public health problem worldwide. It is marked by increased Th2 response resulting in eosinophil accumulation. The pathophysiology of asthma involves various cell types, including epithelial cells, dendritic cells (DCs), innate lymphoid cells (ILCs), B cells, and effector cells. Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor for immune regulation, is known for its role in T cells and, more recently, in myeloid cells. However, the specific contributions of NFATc1 in T cells and DCs in the context of asthma are not well understood. ObjectiveExplore NFATc1’s role in T cells and dendritic cells in modulating Th2 immune responses within the pathophysiology of allergic asthma. MethodsMice lacking Nfatc1 in CD4+T cells or CD11c+ dendritic cells, were induced with asthma using house dust mite (HDM), enabling investigation into NFATc1's role in both cell types in experimental allergic asthma. Additionally, the study examined NFATc1 expression in these cells and its correlation with blood eosinophil levels in an adult asthma cohort. ResultsIn HDM-induced asthma model, we found that Nfatc1 deficiency either in CD4+ T cells or CD11c+ dendritic cells resulted in reduced Th2-driven eosinophilic inflammation, immunoglobulin E (IgE) levels, and mast cell presence in the lung of asthmatic mice. Nfatc1's absence in CD4+ T cells directly hampered Th2 cell polarization and functionality, whereas in CD11c+ dendritic cells, it affected DC differentiation and maturation, thereby weakening T cell priming, proliferation and subsequent Th2 differentiation. Correspondingly, translational research indicated significant correlations between CD4+NFATc1+ and CD11c+NFATc1+ cell populations and eosinophil levels in asthmatic patients, but not in healthy controls. ConclusionNFATc1 in T cells and dendritic cells modulate Th2-mediated eosinophilic inflammation in allergic asthma, which offering insights into asthma pathogenesis and identifying NFATc1 as a potential target for therapeutic intervention.