Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing

Ishino, Takashi; Takeno, Sachio; Takemoto, Kota; Yamato, Kensuke; Oda, Takashi; Nishida, Munehiro; Horibe, Yuichiro; Chikuie, Nobuyuki; Kono, Takashi; Taruya, Takayuki; Hamamoto, Takao; Ueda, Tsutomu

doi:10.3390/ijms23105653

Cited by 10 publications

(11 citation statements)

References 29 publications

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“…Asthma is a heterogeneous pulmonary disease comprised of several different endotypes which depict various pathways of the inflammatory and immune response 38 . In general, most of the current research concentrates on eosinophilic airway inflammation, with poor knowledge of principal causes and mechanisms related to non-eosinophilic phenotypes, which are less receptive to inhaled corticosteroids (ICS), the current treatment of choice for asthma 39 - 41 .…”

Section: Discussionmentioning

confidence: 99%

“…Asthma is a heterogeneous pulmonary disease comprised of several different endotypes which depict various pathways of the inflammatory and immune response [38]. In general, most of the current research concentrates on eosinophilic airway inflammation, with poor knowledge of principal causes and mechanisms related to non-eosinophilic phenotypes, which are less receptive to inhaled corticosteroids (ICS), the current treatment of choice for asthma [39][40][41]. In the present study, we demonstrated that sphingolipid metabolism is abnormal in asthmatic patients, whereas sphingosine metabolites, altered largely in the untargeted lipidomics analysis, failed to distinguish between the different endotypes of asthma both in plasma and induced sputum in the targeted lipidomics analysis.…”

Section: Discussionmentioning

confidence: 99%

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Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Wang¹,

Tian²,

Lu³

et al. 2023

Int. J. Biol. Sci.

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Patients with eosinophilic asthma react well to conventional treatment of asthma while individualized therapy for non-eosinophilic endotypes have yet to be developed. Dysregulated sphingosine metabolites are associated with the pathophysiology of different asthma endotypes with their receptors involved. However, whether the sphingosine-1-phosphate receptor 4 (S1PR4) contributes to disease progression of asthma remains underappreciated. In this study, we demonstrated that sphingosine metabolism was disturbed in asthma while it could not be used to distinguish between different endotypes of asthma. S1PR4, a vital receptor of bioactive sphingosine metabolites and mainly expressed in macrophages, exhibited lower expression both in patients and experimental mice with neutrophilic airway inflammation. Additionally, S1pr4 deficiency aggravated the OVA/LPS-induced pulmonary inflammation in mice along with a significant up-regulation in M1 macrophage activation. Mechanistic studies showed that S1PR4 was strongly connected to bioactive oxylipins concurrent with bounding to formyl peptide receptor 2 to influence the phosphorylation of JNK and contributed to the macrophage M1 program, which in turn secreted amounts of inflammatory cytokines associated to the inflammatory response of neutrophilic asthma. Furthermore, treating mice with S1PR4 agonist CYM50308 was characterized by less pulmonary inflammatory infiltration. Our research indicates S1PR4 a promising therapeutic target for non-eosinophilic phenotypes of asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Wang¹,

Tian²,

Lu³

et al. 2023

Int. J. Biol. Sci.

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“…Specifically among DEGs detected in EoD compared to controls, within CD4 + T there was an upregulation of genes associated with the chronic rhinosinusitis and nasal polyps ( SCGB3A1 and MTRNR2L8 ) (61, 62), and downregulation of IL27RA , whose decreased expression is associated with allergic airway inflammation (63). Within DC cells, there was also dysregulation of genes associated with chronic obstructive pulmonary disorder (COPD) ( LILRA5, IGLC2 , and IGLC3 ) (64, 65).…”

Section: Discussionmentioning

confidence: 99%

Genomic Insights into Pediatric Intestinal Inflammatory and Eosinophilic Disorders using Single-sell RNA-sequencing

Keever-Keigher,

Harvey,

Williams

et al. 2023

Preprint

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Chronic inflammation of the gastrointestinal (GI) tissues underlies GI inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These GI disorders include inflammatory bowel diseases (Crohn’s disease (CD) and ulcerative colitis (UC)), and eosinophilic disorders (eosinophilic esophagitis (EoE) and eosinophilic duodenitis (EoD)). GI inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give a proper diagnosis. This study aims to use peripheral blood mononuclear cells (PBMCs) from individuals with CD, UC, EoE, and EoD to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing (scRNA-seq) was performed on PBMCs isolated from the blood samples of pediatric patients diagnosed with a GI disorder, including CD, UC, EoE, EoD, and controls with histologically healthy gastrointestinal tracts. We identified 1,185 (FDR < 0.05) differentially expressed genes (DEGs) between individuals with GI disorders and controls across six distinct immune cell populations. Few patterns of gene dysregulation were common among all GI disorders, including the downregulation ofESR2in CD4+T cells compared to controls. Many DEGs showed distinct patterns of dysregulation among individuals with CD, UC, EoE, and EoD compared to controls, such as dysregulation of genes associated with oxidative stress in monocytes of individuals CD and the upregulation ofSCGB3A1in CD4+T cells in individuals with EoD. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with CD, UC, EoD, and EoE compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.

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“…RNA was extracted from the same NPs biopsies and RNA-Seq was performed using Illumina HiSeq4000, as described [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Comparing Protein and Gene Expression Signature between Nasal Polyps and Nasal Fluids in Chronic Rhinosinusitis

Hou,

Chen,

et al. 2023

Int Arch Allergy Immunol

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Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a serious inflammatory condition. Nasal fluids (NFs) present a noninvasive alternative to nasal biopsy for studying CRSwNP pathogenesis. We aimed to compare the protein and mRNA inflammation signature between nasal polyps (NPs) and NFs. Method: The performance of polyvinyl alcohol (PVA) sponges and NFs absorbable device (NFAD) for collecting NFs from 20 patients with CRSwNP was compared using the Luminex assay. The other group consisted of four healthy controls and an additional 21 CRSwNP patients (including eosinophilic CRSwNP [ECRSwNP] and non-eosinophilic CRSwNP [NECRSwNP]) for protein quantification by Olink platform and gene expression evaluation by RNA-sequencing. Spearman’s analysis was performed to detect correlations between protein expression levels in NFs and clinical assessment variables. Results: NFAD-collected NFs contained at least a 2-fold higher concentration of cytokines than that obtained using PVA sponge, and these cytokines levels are significantly associated with NPs (ρ > 0.45, p < 0.05). Differentially expressed proteins between NFs and NPs were significantly correlated in the ECRSwNP subgroup compared with controls (ρ = 0.41, p < 0.01). Levels of Th2/IL-13, MCP4, and CCL4, characteristic of eosinophilic infiltration, were increased in ECRSwNP patients. A significant correlation between gene and protein expression was observed (ρ = 0.34, p < 0.01). PDL2 levels in NFs were positively correlated with ECRSwNP postoperative recurrence, the nasal VAS, and SNOT-22 scores (ρ > 0.68, p < 0.05 for all). Conclusion: Our study revealed similarities and discrepancies in inflammatory signatures between NPs and NFs in the same CRSwNP patient.

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Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing

Cited by 10 publications

References 29 publications

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Genomic Insights into Pediatric Intestinal Inflammatory and Eosinophilic Disorders using Single-sell RNA-sequencing

Comparing Protein and Gene Expression Signature between Nasal Polyps and Nasal Fluids in Chronic Rhinosinusitis

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