Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis

Stevens, Whitney W.; Peters, Anju T.; Tan, Bruce K.; Klingler, Aiko I.; Poposki, Julie A.; Hulse, Kathryn E.; Grammer, Leslie C.; Welch, Kevin C.; Smith, Stephanie Shintani; Conley, David B.; Kern, Robert C.; Schleimer, Robert P.; Kato, Atsushi

doi:10.1016/j.jaip.2019.05.009

Cited by 296 publications

(312 citation statements)

References 33 publications

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…Th2 inflammation is commonly associated with CRSwNP, whereas Th1 inflammation is associated with CRSsNP. However, CRS had a combination of Th1, Th2, and other inflammatory patterns with mixed endotypes [15]. ILC2s are increased in CRSwNP or eosinophilic CRS and epithelial cell-derived IL-25, IL-33, and TSLP are the key cytokines to induce Th2 cytokine production by ILC2s [16,17].…”

Section: Discussionmentioning

confidence: 99%

“…The activation of nasal epithelial cells may induce not only Th2 inflammation but also Th1 inflammation in nasal mucosa through the interaction between structural and inflammatory cells. In CRS with or without nasal polyps, although CRSwNP has Th2 dominant and CRSsNP has Th1 dominant endotype characteristics; approximately 30% of CRS had mixed endotypes [15]. In the nasal mucosa, which contains epithelial cells, structural cells, and other inflammatory cells, exogenous pathogenic stimulation simultaneously triggers not only epithelial cells but also structural cells and the produced chemical mediators may have autocrine or paracrine effects, which enhance the inflammatory reaction in the nasal mucosa.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses

Shin

Lee

et al. 2020

IJMS

View full text Add to dashboard Cite

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells’ (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with Alternaria alternata, Aspergillus fumigatus, Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. Alternaria, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-κB, AP-1, and MAPK pathway. NECM induced IL-5, IFN-γ, and TNF-α production from PBMCs, without increasing ILC2 expression. Alternaria and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses

Shin

Lee

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Studies have indicated that CRS is a heterogeneous disease with several unclear endotypes, which are mainly characterized by type 1, 2, and 3 in ammatory patterns [15,[25][26][27]. Furthermore, some recent studies have indicated that the most prevalent endotype in CRSwNP is characterized by type 2 in ammation [28], and that type 2 in ammation in CRSwNP may be differentiated into moderate and severe type 2 in ammatory patterns according to the intensity of in ammation [29].…”

Section: Discussionmentioning

confidence: 99%

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Wang

Luan

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP+AS. Methods: A total of 195 subjects; including 65 CRSwNP+AS patients, 99 patients with CRSwNP-alone, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP+AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions: Patients with CRSwNP+AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

show abstract

“…Olfactory information, processed and integrated in the olfactory bulb, is then projected onto the primary olfactory centers such as the limbic system (emotions) and the hypothalamus (memory) and finally projected to the olfactory cortex where humans acquire consciousness of smelling (Fig 1, A-D). 2 Smell loss in CRS is caused by a multifactorial combination of mechanical obstruction of odorant transmission in the olfactory cleft due to mucosal type 2 inflammation (edema or nasal polyps), 5 leading to shedding and/or degeneration of the olfactory epithelium and causing the reduction or loss of the sense of smell (Fig 1, A, E, F, and G).…”

mentioning

confidence: 99%

The sense of smell in chronic rhinosinusitis

Mullol

Mariño‐Sánchez

Valls

et al. 2020

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis

Cited by 296 publications

References 33 publications

Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses

Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

The sense of smell in chronic rhinosinusitis

Contact Info

Product

Resources

About