Exome variants associated with asthma and allergy

Wjst, Matthias

doi:10.1038/s41598-022-24960-6

Cited by 6 publications

(6 citation statements)

References 53 publications

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“…Among the upregulated genes in Mo/Ma were CXCL13 , a B‐cell chemoattractant, OLFM4 , associated with severe lung disease in humans [44, 45], and CHI3L1 , a marker of neutrophilic asthma (Figure 5d) [21]. S100A8 , known for its increased expression in individuals with steroid‐resistant neutrophilic asthma [46], was upregulated, and so was TLR1 , recently identified as a potential therapeutic target for asthma in humans (Figure 5d) [47].…”

Section: Resultsmentioning

confidence: 99%

Single‐cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Sage,

Leeb,

Jagannathan

et al. 2023

Immunology

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Severe equine asthma (SEA) is a complex respiratory condition characterized by chronic airway inflammation. It shares many clinical and pathological features with human neutrophilic asthma, making it a valuable model for studying this condition. However, the immune mechanisms driving SEA have remained elusive. Although SEA has been primarily associated with a Th2 response, there have also been reports of Th1, Th17, or mixed‐mediated responses. To uncover the elusive immune mechanisms driving SEA, we performed single‐cell mRNA sequencing (scRNA‐seq) on cryopreserved bronchoalveolar cells from 11 Warmblood horses, 5 controls and 6 with SEA. We identified six major cell types, including B cells, T cells, monocytes–macrophages, dendritic cells, neutrophils, and mast cells. All cell types exhibited significant heterogeneity, with previously identified and novel cell subtypes. Notably, we observed monocyte–lymphocyte complexes and detected a robust Th17 signature in SEA, with CXCL13 upregulation in intermediate monocytes. Asthmatic horses exhibited expansion of the B‐cell population, Th17 polarization of the T‐cell populations, and dysregulation of genes associated with T‐cell function. Neutrophils demonstrated enhanced migratory capacity and heightened aptitude for neutrophil extracellular trap formation. These findings provide compelling evidence for a predominant Th17 immune response in neutrophilic SEA, driven by dysregulation of monocyte and T‐cell genes. The dysregulated genes identified through scRNA‐seq have potential as biomarkers and therapeutic targets for SEA and provide insights into human neutrophilic asthma.

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Section: Resultsmentioning

confidence: 99%

Single‐cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Sage,

Leeb,

Jagannathan

et al. 2023

Immunology

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“…A recent study demonstrated that genetic variations in IL1RL1 are strongly associated with asthma, revealing that IL1RL1 acts as an essential driver of type 2 immune responses to IL-33 [ 29 ]. Moreover, IL1RL1 is a reliable marker of Th2 lymphocytes in AR, and IL1RL1 variants (e.g., rs72823628, rs950881, and rs3771175) are associated with AR risk [ 19 , 30 , 31 ]. However, in this study, the association of these variants and others between AR1 and AR2 was not identified, which is a limitation of this study and should be confirmed in the near future.…”

Section: Discussionmentioning

confidence: 99%

Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response

Jeon

Kang

Lee

et al. 2023

BioMed Research International

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This study is aimed at investigating the potential molecular features of allergic rhinitis (AR) and identifying gene signatures and related transcription factors using transcriptome analysis and in silico datasets. Transcriptome profiles were obtained using three independent cohorts (GSE101720, GSE19190, and GSE46171) comprising healthy controls (HC) and patients with AR. The pooled dataset ( n = 82 ) was used to identify the critical signatures of AR compared with HC. Subsequently, key transcription factors were identified by a combined analysis using transcriptome and in silico datasets. Gene ontology: bioprocess (GO: BP) analysis using differentially expressed genes (DEGs) revealed that immune response-related genes were significantly enriched in AR compared with HC. Among them, IL1RL1, CD274, and CD44 were significantly higher in AR patients. We also identified key transcription factors between HC and AR using the in silico dataset and found that AR samples frequently express KLF transcription factor 4 (KLF4), which regulates immune response-related genes including IL1RL1, CD274, and CD44 in human nasal epithelial cells. Our integrative analysis of transcriptomic regulation provides new insights into AR, which may help in developing precision management for patients with AR.

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“…Among the upregulated genes in Mo/Ma were CXCL13, a B-cell chemoattractant, OLFM4, associated with severe lung disease in humans [44,45], and CHI3L1, a marker of neutrophilic asthma (Figure 5d) [21]. S100A8, known for its increased expression in individuals with steroid-resistant neutrophilic asthma [46], was upregulated, and so was TLR1, recently identified as a potential therapeutic target for asthma in humans (Figure 5d) [47].…”

Section: Genes Associated With T-cell Function Are Dysregulated In Seamentioning

confidence: 99%

Single-cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Sage

Leeb

Jagannathan

et al. 2023

Preprint

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Severe equine asthma (SEA) shares clinical and pathological features with human neutrophilic asthma, serving as a rare natural model for this condition. To uncover the elusive immune mechanisms driving SEA, we performed single-cell mRNA sequencing (scRNA-seq) on cryopreserved bronchoalveolar cells from 11 Warmblood horses, five controls and six with SEA. We identified six major cell types, showing significant heterogeneity and novel subtypes. Notably, we observed monocyte-lymphocyte complexes and detected a robust Th17 signature in SEA, with CXCL13 upregulation in intermediate monocytes. Asthmatic horses exhibited expansion of the B cell population, Th17 polarization of the T cell populations, and dysregulation of genes associated with T cell function. Neutrophils demonstrated enhanced migratory capacity and heightened aptitude for neutrophil extracellular trap formation. These findings provide compelling evidence for a predominant Th17 immune response in neutrophilic SEA, driven by dysregulation of monocyte and T cell genes. The dysregulated genes identified through scRNA-seq have potential as biomarkers and therapeutic targets for SEA and provide insights into human neutrophilic asthma.

show abstract

Exome variants associated with asthma and allergy

Cited by 6 publications

References 53 publications

Single‐cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Single‐cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response

Single-cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

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