Dataset Information

Type 2/Th2-driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model.

ABSTRACT:

Background

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic inflammatory disease often accompanied by impairment of sense of smell. This symptom has been somewhat overlooked, and its relationship to inflammatory cytokines, tissue compression, neuronal loss, and neurogenesis is still unclear.

Methods

In order to elucidate potential mechanisms leading to CRS in humans, we have established a type 2/T helper type 2 cell (Th2)-mediated allergic CRS mouse model, based on house dust mite (HDM) and Staphylococcus aureus enterotoxin B (SEB) sensitization. The inflammatory status of the olfactory epithelium (OE) was assessed using histology, biochemistry, and transcriptomics. The sense of smell was evaluated by studying olfactory behavior and recording electro-olfactograms (EOGs).

Results

After 22 weeks, a typical type 2/Th2-mediated inflammatory profile was obtained, as demonstrated by increased interleukin (IL)-4, IL-5, and IL-13 in the OE. The number of mast cells and eosinophils was increased, and infiltration of these cells into the olfactory mucosa was also observed. In parallel, transcriptomic and histology analyses indicated a decreased number of immature olfactory neurons, possibly due to decreased renewal. However, the number of mature sensory neurons was not affected and neither the EOG nor olfactory behavior was impaired.

Conclusion

Our mouse model of CRS displayed an allergic response to HDM + SEB administration, including the type 2/Th2 inflammatory profile characteristic of human eosinophilic CRSwNP. Although the sense of smell did not appear to be altered in these conditions, the data reveal the influence of chronic inflammation on olfactory neurogenesis, suggesting that factors unique to humans may be involved in CRSwNP-associated anosmia.

SUBMITTER: Rouyar A

PROVIDER: S-EPMC6590422 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Type 2/Th2-driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model.

Rouyar Angela A Classe Marion M Gorski Raphael R Bock Marie-Dominique MD Le-Guern Joelle J Roche Sandrine S Fourgous Valerie V Remaury Anne A Paul Pascal P Ponsolles Clara C Françon Dominique D Rocheteau-Beaujouan Laurence L Clément Margerie M Haddad El-Bdaoui EB Guillemot Jean-Claude JC Didier Michel M Biton Bruno B Orsini Cecile C Mikol Vincent V Leonetti Maud M

Allergy 20181216 3

<h4>Background</h4>Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic inflammatory disease often accompanied by impairment of sense of smell. This symptom has been somewhat overlooked, and its relationship to inflammatory cytokines, tissue compression, neuronal loss, and neurogenesis is still unclear.<h4>Methods</h4>In order to elucidate potential mechanisms leading to CRS in humans, we have established a type 2/T helper type 2 cell (Th2)-mediated allergic CRS mouse model, base ...[more]

PMID: 29987849

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Project description:PurposeThe Toll-like receptor 9 (TLR9) signaling pathway is involved in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyposis. The aim of this study was to assess the therapeutic potential of the TLR9 pathway inhibitor chloroquine in CRS mice.MethodsThe expression of type I interferons (IFNs) in human CRS tissues was evaluated using quantitative polymerase chain reaction (qPCR), western blotting, and immunofluorescence. Mice were divided into 4 treatment groups: the control, nasal polyp (NP), chloroquine treatment (NP + Chlq), and dexamethasone treatment (NP + Dexa) groups. The effects of chloroquine on polyp formation and mucosal inflammation were examined by hematoxylin and eosin staining. The expression levels of type I IFN, B-cell activating factor (BAFF), TLR9, high mobility group box 1 (HMGB1), and proinflammatory cytokine expression levels were assessed using qPCR, western blot, or enzyme-linked immunosorbent assay.ResultsIFN-α and IFN-β mRNA levels were significantly higher in patients with eosinophilic NPs (EPs) than in healthy individuals or non-EP patients. The polyp score, epithelial thickness, mucosal thickness, and the number of eosinophils in nasal mucosa were significantly higher in the NP group compared with the control, NP + Chlq, and NP + Dexa groups. NP + Chlq or NP + Dexa significantly suppressed the induction of type I IFN and BAFF expression in the NP group; these treatments also significantly suppressed the induction of TLR9, HMGB1, interferon regulatory factors, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and Th cytokine expression in the NP group. The secreted levels of anti-dsDNA Immunoglobulin G (IgG) were significantly higher in the NP group than in the control, NP + Chlq, and NP + Dexa groups. There were significant positive correlations between BAFF and mRNA levels of IFN-α/β/the protein levels of anti-dsDNA IgG.ConclusionsChloroquine may be used for the treatment of patients with eosinophilic CRS.

Project description:ObjectivesPrior studies have indicated that olfactory cleft (OC) opacification correlates with olfaction in patients with chronic rhinosinusitis (CRS). However, the results have been unclear in patients without polyps. The purpose of this study was to further explore the relationship between OC opacification, sinus opacification, and olfactory function in patients with CRS.MethodsOne hundred and forty-eight patients with CRS were prospectively enrolled across five institutions. Olfactory function was evaluated using the Sniffin' Sticks tests (Burghardt, Wedel, Germany) and the 17-item Questionnaire of Olfactory Disorders (QOD-NS). Computed tomography (CT) scans for each patient were acquired and Lund-Mackay scores recorded. Opacification of the OC was determined using OsiriX MD (Pixmeo, Bernex, Switzerland) and correlated with olfaction scores.ResultsA total of 148 CRS patients, 73 CRS without nasal polyps (CRSsNP) and 75 CRS with nasal polyps (CRSwNP), as well as 30 control subjects were enrolled. Overall OC opacification averaged 63.7% in CRS patients and 47.1% in control subjects (P < 0.001). In the overall cohort, OC opacification significantly correlated with threshold, discrimination, and identification (TDI) (r = -0.520; P < 0.001) and QOD-NS scores (r = 0.374; P < 0.001). CRSwNP patients demonstrated a significant correlation between OC opacification and TDI scores (r = -0.464; P < 0.001) but not the CRSsNP group (r = -0.143; P = 0.229). Lund-Mackay score correlated with TDI in both the CRSsNP (r = -0.300; P = 0.010) and CRSwNP (r = -0.271; P = 0.019) groups.ConclusionCT opacification is associated with olfactory dysfunction differentially based on nasal polyp status. Smell loss in CRSwNP correlated with both OC opacification and Lund-Mackay score, whereas CRSsNP correlated only with Lund-Mackay score, indicating different relationships between olfactory function and local inflammatory processes in these disorders.Level of evidence2 Laryngoscope, 130:2311-2318, 2020.

Dataset Information

Type 2/Th2-driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model.

Background

Methods

Results

Conclusion

Publications

Type 2/Th2-driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model.

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