The relation between Schneiderian membrane thickening and radiodiagnostic features of periapical pathology.

This study aimed to assess the relationship between Schneiderian membrane thickening and periapical pathology in a retrospective analysis of Cone Beam Computed Tomography (CBCT) images. For this, 147 CBCT scans containing 258 sinuses and 1,181 teeth were assessed. Discontinuation of the lamina dura, widening of the periodontal ligament space, apical periodontitis (AP), and partly demineralized maxillary sinus floor associated with AP were considered periapical pathology. Maxillary sinus mucosal thickening (MSMT) was classified as odontogenic or non-odontogenic. An irregular band with a focal tooth associated thickening and local thickening related to a root were considered odontogenic types of MSMT. The relation between the imaging features of periapical pathology and the type and thickness of MSMT was determined by logistic regression and linear mixed model, respectively. In addition, linear regression and Mann Whitney test evaluated the relation and demineralization of the AP lesion towards the sinus floor (p≤0.05). The odds of having an odontogenic type of MSMT were significantly higher when a periapical pathology was present in the maxillary sinus. Eighty-two percent of AP partly demineralized towards the sinus floor were associated with an odontogenic MSMT. Both AP lesions partly demineralized towards the sinus floor and, with increased diameter, led to increased MSMT. In conclusion, there is an 82% risk of having an odontogenic type of MSMT with the presence of AP partly demineralized towards the sinus floor. More thickening of the maxillary sinus mucosa is seen with larger AP lesions and partial demineralization of the sinus floor.

The effect of adipose tissue-derived stromal vascular fraction/gel material on wound healing in a rat model of nasal mucosa injury.

BACKGROUND: Stromal Vascular fraction/gel (SVF/gel) is prepared mechanically from autologous adipose tissue, and it is known for its regenerative and anti-inflammatory properties. AIMS: To assess histopathological effects of adipose tissue-derived SVF/gel and nasal steroids on nasal mucosal healing. MATERIAL AND METHODS: Forty-two Wistar Albino rats with right nasal mucosal injury were randomly divided into three groups: control (saline), Mometasone Furoate (MF), and SVF/gel. Control group (n = 14) received saline for 7 days, while MF group (n = 14) was administered MF to the right nasal cavity for 7 days. SVF/gel group (n = 14) was treated once with SVF/gel in the right nasal cavity. Histological analysis on days 14 and 28 post-injury focused on evaluating epithelial thickness, inflammation, disarray, subepithelial thickness, goblet cell count, subepithelial fibrosis, presence of ciliated cells, lacunae, adhesion, and neo-osteogenesis. RESULTS: When comparing the MF and SVF/gel groups, statistically significant differences were found on day 14 in indices of epithelial thickness, subepithelial thickness, goblet cells, subepithelial fibrosis, and ciliated cells. On day 28, SVF/gel group exhibited higher ciliated cell counts and lower subepithelial fibrosis values (p = .027; p = .016). Additionally, epithelial disarray, adhesions, lacunae, and neo-osteogenesis were not observed in the SVF/gel group. CONCLUSIONS AND SIGNIFICANCE: SVF/gel accelerates re-epithelialization, reduces fibrosis and adhesions, and enhances cilia formation compared to nasal steroids. These findings suggest that SVF/gel is an autologous and cost-effective treatment for improving nasal mucosal healing post-injury.

Effects of Benzo[α]pyrene on Mucus Secretion and Tissue Remodeling in a Rat Model of Allergic Rhinitis.

OBJECTIVES: Exposure to benzo[α]pyrene (BaP) increases the incidence and severity of allergic rhinitis (AR), but the underlying mechanisms remain unclear. Thus, we investigated the in vivo effects of BaP exposure on mucus hypersecretion and tissue remodeling in a rat model of AR. METHODS: Female Sprague-Dawley rats were randomly divided into 4 groups: a negative control group, a group of healthy rats exposed to BaP, a group of rats with ovalbumin (OVA)-induced AR, and a group of AR model rats exposed to BaP. Nasal symptoms and levels of OVA-specific serum immunoglobulin E (IgE) were measured in each individual rat. Moreover, examination of goblet cell hyperplasia and collagen deposition was carried out with periodic acid-Schiff (PAS) staining and Masson trichrome (MT) staining. Mucin 5AC (MUC5AC) expression was assessed by immunohistochemistry. RESULTS: BaP significantly increased the number of sneezes, the number of nasal rubs and the levels of OVA-specific serum IgE in rats with AR. Statistically significant differences in goblet cell hyperplasia and collagen deposition were observed between the BaP-exposed AR model group and the AR model group. Immunohistochemical results showed that the nasal mucosa of AR model rats displayed markedly elevated MUC5AC expression after BaP exposure. CONCLUSION: Our data indicate that mucus hypersecretion and the development of nasal remodeling might be pathophysiologic mechanisms underlying increased susceptibility to AR after exposure to BaP.

Rare presence and function of neuroendocrine cells in the nasal mucosa.

There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR. The expression of typical NECs markers, CHGA, ASCL1 and CGRP, were evaluated on gene and protein level in human samples using real-time quantitative PCR (RT-qPCR), western blot, immunohistochemistry fluorescence staining, RNA scope assay, flow cytometry and single cell RNA-sequencing. Furthermore, the change in peak nasal inspiratory flow after cold dry air provocation and visual analogue scale scores were used to evaluate NHR or disease severity, respectively. Limited gene expression of the NECs markers CHGA and ASCL1 was measured in patients with upper airway diseases and controls. Gene expression of these markers did not correlate with NHR severity nor disease severity. In vitro, CHGA and ASCL1 expression was also evaluated in primary nasal epithelial cell cultures from patients with upper airway disease and controls using RT-qPCR and western blot. Both on gene and protein level only limited CHGA and ASCL1 expression was found. Additionally, NECs were studied in nasal biopsies of patients with upper airway diseases and controls using immunohistochemistry fluorescence staining, RNA scope and flow cytometry. Unlike in ileum samples, CHGA could not be detected in nasal biopsies of patients with upper airway diseases and control subjects. Lastly, single cell RNA-sequencing of upper airway tissue could not identify a NEC cluster. In summary, in contrast to the bronchi and gut, there is only limited evidence for the presence of NECs in the nasal mucosa, and without correlation with NHR, thereby questioning the relevance of NECs in upper airway pathology.

Comparison of Short-term Outcomes Between Schneiderian Membrane Perforation and Non-perforation Patients after Simultaneous External Elevation and Implantation.

PURPOSE: To compare short-term outcomes between membrane perforation and non-perforation patients after simultaneous external elevation with implantation. MATERIALS AND METHODS: In this retrospective observational study, 60 maxillary posterior tooth-loss patients with an insufficient amount of residual bone for direct implantation were enrolled. All patients underwent simultaneous external elevation and implantation, and were divided into perforation and non-perforation groups according to the postoperative Schneiderian membrane status. RESULTS: Of the 60 patients, 30 cases (35 implants) were assigned to the membrane perforation group, and 30 (44 implants) were allocated to the non-perforation group. There were no statistically significant differences in baseline data (p>0.05). In the perforation group, the mean vertical bone gain (VBG) at 6 and 12 months was 6.02±2.14 mm and 5.37±2.22 mm, resp., compared to 6.78±2.59 mm and 6.42±2.64 mm in the non-perforation group, resp. (both p>0.05). Preoperative median Schneiderian membrane thickness (SMT) in the perforation group was 0.77 mm, which was statistically significantly thinner than the 1.24 mm measure in the non-perforation group (p< 0.05); however, there was no statistically significant difference between two groups at 12 months postoperatively (0.80 mm vs 1.25 mm, p>0.05). The marginal bone loss at 1 year after implant restoration in the perforation and non-perforation groups was 0.16±0.10 mm and 0.22±0.12 mm, resp. During postoperative follow-up, the implant survival rate was 100% in the two groups. The incidence of postoperative nasal bleeding in the perforation group was statistically significantly higher compared with that in the non-perforation group (50% vs 16.7%, p<0.05), whereas no statistically significant differences were observed in the incidence of facial swelling, intraoral bleeding, wound dehiscence and acute/chronic sinusitis between the two groups (p>0.05). CONCLUSIONS: Schneiderian membrane perforation after simultaneous external elevation and implantation do not adversely affect short-term clinical and radiographic outcomes.

Mucosal LTE4, PGD2 and 15(S)-HETE as potential prognostic markers for polyp recurrence in chronic rhinosinusitis.

BACKGROUND: Altered biosynthesis of eicosanoids is linked to type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP), but their role in recalcitrant NPs is unclear. OBJECTIVES: We sought to identify endotypes that are linked to recalcitrant CRSwNP, based on eicosanoids, their biosynthetic enzymes, and receptors as well as cytokines and the presence of eosinophils and mast cells in recurrent NPs. METHODS: Mucosal tissue collected at the time of sinus surgery from 54 patients with CRSwNP and 12 non-CRS controls were analysed for leukotriene (LT) E4, prostaglandin (PG) D2, 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and 17 cytokines with ELISAs and Bio-Plex immunoassays. Patient subgroups were identified by cluster analysis and the probability of NP recurrence were tested with logistic regression analyses. Gene expressions were analysed with qPCR. Tryptase and eosinophil-derived neurotoxin (EDN) were measured with ELISAs as indications of the presence of mast cells and eosinophils, respectively. RESULTS: Clustering of patients showed that an inflammatory signature characterised by elevated LTE4, PGD2, 15(S)-HETE and IL-13 was associated with NP recurrence. Previous NP surgery as well as aspirin-exacerbated respiratory disease were significantly more common among these patients. Expression of cyclooxygenase 1 was the only gene associated with NP recurrence. Levels of EDN, but not tryptase, were significantly higher in patients with recurrent NPs. CONCLUSION: Distinguishing endotypes that include LTE4, PGD2, 15HETE and conventional biomarkers of type 2 inflammation could help predict recurrent nasal polyposis and thus identify cases of recalcitrant CRSwNP.

Langerhans Cell Histiocytosis of the Nasal Mucosa.

This case report describes a female patient in her early 40s with left-sided cervical lymphadenopathy, facial swelling, nasal congestion, and a left nasal mass.

The role of revision sinus surgery in the initiation of dupilumab therapy: A real-world study of molecular and cellular features.

KEY POINTS: A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long-term interleukin (IL)-4/IL-13 tissue mRNA. Pre-dupilumab revision surgery is associated with reduced tissue eosinophils and GATA-3+ cells.

ROS responsive hydrogel for inhibition of MUC5AC against allergic rhinitis: A new delivery strategy for Ipratropium Bromide.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. The bothersome symptoms of AR, such as runny nose and nasal congestion, affect millions of people worldwide. Ipratropium Bromide (IB), commonly used in clinical practice for treating AR, requires frequent administration through nasal spray and may cause significant irritation to the nasal mucosa. The induction of ROS is closely related to the initiation and symptoms of AR, and ROS will continue to accumulate during the onset of AR. To address these challenges, we have designed a drug delivery system that can be administered in liquid form and rapidly crosslink into a ROS-responsive gel in the nasal cavity. This system enables sustained ROS responsive release of IB in a high-concentration ROS environment at AR lesions, thereby alleviating AR symptoms. The gel demonstrated prolonged release of IB for up to 24 hours in rats. In the treatment of AR rat models, it improved their symptoms, reduced the expression of various inflammatory factors, suppressed MUC5AC protein expression, and decreased mucus secretion through a ROS responsive IB release pattern. Overall, this system holds promise as a better option for AR treatment and may inspire the design of nanogel-based nasal drug delivery systems.

Endoscopic resection of primary sinonasal mucosal melanoma with orbital invasion: How I do it.

Primary sinonasal mucosal melanoma is a rare aggressive malignancy. In this video, a case of a 68-year-old female who presented with diplopia for 2 weeks is described. The present video reports the endoscopic endonasal surgical excision of a primary sinonasal mucosal melanoma. The video contains patient's medical history, preoperative radiological evaluations and step-by-step description of surgical steps of the procedure with the utilization of computer-assisted navigation system.

Expression of immune checkpoint molecules TIGIT and TIM-3 by tumor-infiltrating lymphocytes predicts poor outcome in sinonasal mucosal melanoma.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a rare but aggressive tumor with a poor prognosis. The co-inhibitory receptors T cell immunoglobulin and mucinodomain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) are promising new targets in anti-cancer immunotherapy. The expression profiles of these immune checkpoint molecules (ICMs) and potential prognostic implications have not been characterized in SNMM yet. METHODS: Immunohistochemical staining for TIGIT, LAG-3 and TIM-3 was performed on tumor tissue samples from 27 patients with primary SNMM. Associations between ICM expression and demographic parameters, AJCC tumor stage, overall survival, and recurrence-free survival were retrospectively analyzed. RESULTS: SNMM patients with low numbers of TIGIT+ and TIM-3+ tumor infiltrating lymphocytes (TILs) in the primary tumor survived significantly longer than patients with a high degree of TIGIT+ and TIM-3+ TILs. High infiltration with TIM-3+ or TIGIT+ lymphocytes was associated with the higher T4 stage and decreased 5-year survival. CONCLUSION: We identified high densities of TIM-3+ and TIGIT+ TILs as strong negative prognostic biomarkers in SNMM. This suggests that TIM-3 and TIGIT contribute to immunosuppression in SNMM and provides a rationale for novel treatment strategies based on this next generation of immune checkpoint inhibitors. Prospective studies with larger case numbers are warranted to confirm our findings and their implications for immunotherapy.

m6A mRNA methylation-mediated MAPK signaling modulates the nasal mucosa inflammatory response in allergic rhinitis.

Background: Allergic rhinitis (AR) is a complex disease in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications, such as N6-methyladenosine (m6A) modification of mRNA, play important roles in regulating gene expression in multiple physiological and pathological processes. However, the function of m6A modification in AR and the inflammatory response is poorly understood. Methods: We used the ovalbumin (OVA) and aluminum hydroxide to induce an AR mouse model. Nasal symptoms, histopathology, and serum cytokines were examined. We performed combined m6A and RNA sequencing to analyze changes in m6A modification profiles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylated RNA immunoprecipitation sequencing qPCR (MeRIP-qPCR) were used to verify differential methylation of mRNAs and the m6A methylation level. Knockdown or inhibition of Alkbh5 in nasal mucosa of mice was mediated by lentiviral infection or IOX1 treatment. Results: We showed that m6A was enriched in a group of genes involved in MAPK signaling pathway. Moreover, we identified a MAPK pathway involving Map3k8, Erk2, and Nfκb1 that may play a role in the disrupted inflammatory response associated with nasal inflammation. The m6A eraser, Alkbh5, was highly expressed in the nasal mucosa of AR model mice. Furthermore, knockdown of Alkbh5 expression by lentiviral infection resulted in high MAPK pathway activity and a significant nasal mucosa inflammatory response. Our findings indicate that ALKBH5-mediated m6A dysregulation likely contributes to a nasal inflammatory response via the MAPK pathway. Conclusion: Together, our data show that m6A dysregulation mediated by ALKBH5, is likely to contribute to inflammation of the nasal mucosa via the MAPK signaling pathway, suggesting that ALKBH5 is a potential biomarker for AR treatment.

Primary mucosal malignant melanoma (PMMM) of nasal cavity: A report of two cases.

ABSTRACT: Primary mucosal malignant melanoma of the nasal cavity is a rare tumor with aggressive behavior and a dismal prognosis. An extremely rare tumor that accounts for 0.7% to 1% of all melanomas in Caucasian populations and between 4% and 8% of malignant tumors of the nasal cavity and paranasal sinuses. Taking into account the rarity, it is important to note that malignant melanoma should be considered when making a differential diagnosis of tumors of the nose and paranasal sinuses. Two cases of primary malignant melanoma of the nasal cavity both arising in females, one in a 60-year-old and the other in a 64-year-old, both of whom presented with nasal obstruction and brief symptomatic epistaxis are being presented here. The diagnosis being confirmed by a histopathological examination along with an immunohistochemical analysis by using S100 and HMB45.

Rat nasal mucosa-derived ectodermal mesenchymal stem cells: A new therapeutic option for chronic rhinosinusitis.

OBJECTIVE: To investigate the effect of nasal mucosa-derived ectodermal mesenchymal stem cells (NM-EMSCs) on the inflammatory state of rats with chronic rhinosinusitis (CRS) and the underlying therapeutic mechanism. METHODS: NM-EMSCs were isolated and extracted to construct a rat model of CRS. Fifteen Sprague‒Dawley (SD) rats were randomly divided into three groups: CK + NS group rats were injected locally with saline in the nasal mucosa; CRS + NS group rats were injected locally with saline in the nasal mucosa; and CRS + EMSCs group rats were injected locally with NM-EMSCs in the nasal mucosa. One rat from the CRS + EMSCs group was randomly euthanized at 2, 4, and 6 days after injection, and the nasal mucosa tissues were collected for HE staining, Masson's trichrome staining, and periodic acid-Schiff staining. RESULTS: NM-EMSCs specifically expressing CD73, CD105, and CD90 were successfully isolated from the nasal mucosa of rats and were able to differentiate into adipocytes, osteoblasts, and chondrocytes. After saline and NM-EMSC injection, compared with those in the blank control CK + NS group, the nasal mucosa in the CRS + NS and CRS + EMSC groups exhibited obvious thickening, a large amount of inflammatory cell infiltration, and increased collagen and mucin distribution. Four days post-NM-EMSC injection, the thickening of the nasal mucosa in the CRS group was gradually alleviated, the inflammatory cell infiltration gradually decreased, and the distribution of collagen and mucin and the collagen-positive area gradually decreased. Moreover, only a small number of inflammatory cells were visible, and the distribution of mucins was limited to 6 days post-NM-EMSC injection. CONCLUSION: NM-EMSCs effectively attenuated inflammation in the nasal mucosa of CRS model rats.

The Role of Neuro-Immune Interactions in the Pathology and Pathogenesis of Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a non-infectious inflammatory disease of the nasal mucosa mediated by IgE and involving a variety of immune cells such as mast cells. In previous studies, AR was considered as an isolated disease of the immune system. However, recent studies have found that the nervous system is closely related to the development of AR. Bidirectional communication between the nervous and immune systems plays an important role in AR. SUMMARY: The nervous system and immune system depend on the anatomical relationship between nerve fibers and immune cells, as well as various neurotransmitters, cytokines, inflammatory mediators, etc. to produce bidirectional connections, which affect the development of AR. KEY MESSAGES: This article reviews the impact of neuro-immune interactions in AR on the development of AR, including neuro-immune cell units.

Relationship of the accessory maxillary ostium to mucosal thickening and maxillary sinus cysts: a 3D segmentation study.

OBJECTIVES: We aimed to investigate the relationship between the presence of the accessory maxillary ostium (AMO) with mucosal thickening (MT) and maxillary sinus cysts (MSCs). STUDY DESIGN: This single-center retrospective study included patients who underwent paranasal sinus computed tomography (CT) between November 2022 and February 2023. We excluded patients with natural maxillary ostium (NMO) occlusion. Two radiologists evaluated the presence of AMOs, MT, and MSCs in CT images and measured their dimensions using a three-dimensional volumetric analysis program. RESULTS: We included 125 patients (mean age: 36.47 ± 16.0 years; male/female: 67/58). In total, 65 patients (52%) had single or multiple AMOs. No significant relationship was found between the presence of an AMO and the presence of MT on either side (P ≥ .306). There was a statistically significant difference between the presence of an AMO and MSC on the right side (P = .002), but not on the left side (P = .477). The diameter of the AMO and the distance from the AMO to the maxillary sinus floor were not correlated with mucosal thickness or MSC volume, but the distance from the AMO to the sinus floor had a small positive correlation with total maxillary sinus volume. CONCLUSIONS: The presence of an AMO and its increased diameter may not contribute to ipsilateral maxillary sinusitis in patients whose unilateral or bilateral NMOs are not occluded.

Long non-coding RNA NEAT1 exacerbates NLRP3-mediated pyroptosis in allergic rhinitis through regulating the PTBP1/FOXP1 cascade.

BACKGROUND: Allergic Rhinitis (AR) is a prevalent chronic non-infectious inflammation affecting the nasal mucosa. NLRP3-mediated pyroptosis of epithelial cells plays a pivotal role in AR pathogenesis. Herein, we evaluated the impact of the long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) on NLR family pyrin domain containing 3 (NLRP3)-mediated pyroptosis in AR. METHODS: Nasal inflammation levels in ovalbumin (OVA)-induced AR mice were assessed using HE staining, and NLRP3 expression was evaluated through immunohistochemistry. ELISA was utilized to detect OVA-specific IgE, IL-6, IL-5, and inflammatory cytokines (IL-1ß, IL-18). Human nasal epithelial cells (HNEpCs) stimulated with IL4/IL13 were used to analyze the mRNA and protein levels of associated genes utilizing RT-qPCR and western blot, respectively. Cell viability and pyroptosis were assessed by CCK-8 and flow cytometry. The targeting relationship between NEAT1, PTBP1 and FOXP1 were analyzed by RIP and RNA pull down assays. FISH and IF analysis were performed to assess the co-localization of NEAT1 and PTBP1. RESULTS: In both the AR mouse and cellular models, increased levels of NEAT1, PTBP1 and FOXP1 were observed. AR mice exhibited elevated inflammatory infiltration and pyroptosis, evidenced by enhanced expressions of OVA-specific IgE, IL-6, and IL-5, NLRP3, Cleaved-caspase 1, GSDMD-N, IL-1ß and IL-18. Functional assays revealed that knockdown of PTBP1 or NEAT1 inhibited pyroptosis while promoting the proliferation of IL4/IL13-treated HNEpCs. Mechanistically, NEAT1 directly interacted with PTBP1, thereby maintaining FOXP1 mRNA stability. Rescue assays demonstrated that FOXP1 upregulation reversed the inhibitory effects of silencing NEAT1 or PTBP1 on IL4/IL13-stimulated pyroptosis activation in HNEpCs. CONCLUSION: NEAT1 acts as a RNA scaffold for PTBP1, activating the PTBP1/FOXP1 signaling cascade, subsequently triggering NLRP3-mediated pyroptosis in HNEpCs, and ultimately promoting AR progression. These findings highlight some new insights into the pathogenesis of AR.

Changing Characteristics of Treg/Th17 Cells in the Nasal Mucosa of a Mouse Model of Allergic Rhinitis and the Effect of Intervention with Anti-IL-17 Antibody.

BACKGROUND: The incidence rate of allergic rhinitis (AR) is on the rise, which seriously affects the quality of life, work efficiency, mental state of patients, and sleeping in AR sleep. This experiment aimed to investigate the changes in Treg/Th17 cells in the nasal mucosa of an AR mouse model and the intervention effect of an Anti-IL-17 antibody. METHODS: A mouse model of AR was induced by intraperitoneal ovalbumin (OVA) injection for sensitization and stimulation with nasal drops. The times of rubbing, sneezing, and symptomatology scores were counted and analyzed. Pathological damage to the nasal mucosa was observed by Hematoxylin-Eosin (HE) staining. Peripheral blood CD4+CD25+CD127- Treg cell levels and the content of Th17 cells were measured by flow cytometry (FCM). ELISA kits were used to detect the levels of relevant cytokines (IL-10 and TGF-ß1) secreted by Treg cells. The intervention effect of Anti-IL-17 antibody was observed by giving Anti-IL-17 antibody treatment. RESULTS: The times of rubbing, sneezing, and symptomatology scores were significantly higher in mice in the OVA group than in the Control group (p < 0.001). The percentage of CD4+CD25+CD127- Treg cells in CD4+CD25+ T cells (p < 0.05) and the levels of IL-10 (p < 0.001) and TGF-ß1 (p < 0.001) were significantly decreased. After OVA induction, the continuity of the nasal mucosa of mice was interrupted, the percentage of Th17 cells, IL-17, and IL-4 levels were increased, and IFN-γ levels were significantly reduced (p < 0.001). And protein expression of RORγt was significantly upregulated (p < 0.001). In addition, all of these results were reversed by Anti-IL-17 antibody treatment, significantly improving AR-related symptoms (p < 0.05). CONCLUSION: Anti-IL-17 antibodies may regulate the body's immune response by promoting CD4+CD25+CD127- Treg cell differentiation, thereby ameliorating the symptoms associated with AR.

ALOX15+ M2 macrophages contribute to epithelial remodeling in eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Epithelial remodeling is a prominent feature of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP), and infiltration of M2 macrophages plays a pivotal role in the pathogenesis of eCRSwNP, but the underlying mechanisms remain undefined. OBJECTIVE: We sought to investigate the role of ALOX15+ M2 macrophages in the epithelial remodeling of eCRSwNP. METHODS: Digital spatial transcriptomics and single-cell sequencing analyses were used to characterize the epithelial remodeling and cellular infiltrate in eCRSwNP. Hematoxylin and eosin staining, immunohistochemical staining, and immunofluorescence staining were used to explore the relationship between ALOX15+ M2 (CD68+CD163+) macrophages and epithelial remodeling. A coculture system of primary human nasal epithelial cells (hNECs) and the macrophage cell line THP-1 was used to determine the underlying mechanisms. RESULTS: Spatial transcriptomics analysis showed the upregulation of epithelial remodeling-related genes, such as Vimentin and matrix metalloproteinase 10, and enrichment of epithelial-mesenchymal transition (EMT)-related pathways, in the epithelial areas in eCRSwNP, with more abundance of epithelial basal, goblet, and glandular cells. Single-cell analysis identified that ALOX15+, rather than ALOX15-, M2 macrophages were specifically highly expressed in eCRSwNP. CRSwNP with high ALOX15+ M2THP-1-IL-4+IL-13 macrophages had more obvious epithelial remodeling features and increased genes associated with epithelial remodeling and integrity of epithelial morphology versus that with low ALOX15+ M2THP-1-IL-4+IL-13 macrophages. IL-4/IL-13-polarized M2THP-1-IL-4+IL-13 macrophages upregulated expressions of EMT-related genes in hNECs, including Vimentin, TWIST1, Snail, and ZEB1. ALOX15 inhibition in M2THP-1-IL-4+IL-13 macrophages resulted in reduction of the EMT-related transcripts in hNECs. Blocking chemokine (C-C motif) ligand 13 signaling inhibited M2THP-1-IL-4+IL-13 macrophage-induced EMT alteration in hNECs. CONCLUSIONS: ALOX15+ M2 macrophages are specifically increased in eCRSwNP and may contribute to the pathogenesis of epithelial remodeling via production of chemokine (C-C motif) ligand 13.