Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps—A Systematic Review

Palacios-García, José María; Porras-González, Cristina; Moreno‐Luna, Ramón; Maza‐Solano, Juan; Polo-Padillo, Juan; Muñoz-Bravo, José Luis; Sánchez‐Gómez, Serafín

doi:10.3390/jcm12093280

Cited by 3 publications

(1 citation statement)

References 122 publications

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“…Increased protein levels of S100A8, S100A9, and S100A8/A9, were demonstrated in the nasal polyp tissues of CRSwNP patients compared to those in the IT tissues of controls, suggesting evident neutrophil recruitment in CRSwNP 9 . Previous studies have demonstrated that cytokines derived from epithelial cells and stromal cells facilitate neutrophilic inflammation in CRS 10,11 . Nevertheless, specific cell types that secrete these factors and drive neutrophilic inflammation in CRSwNP remain ill-defined.…”

Section: Introductionmentioning

confidence: 96%

Transdifferentiation of epithelial cells and fibroblasts induced by IL-1β fuels neutrophil recruitment in chronic rhinosinusitis

Xie,

Wang,

Jin

et al. 2024

Preprint

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Neutrophilic inflammation contributes to multiple chronic inflammatory airway diseases, including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), and is associated with an unfavorable prognosis. Here, using single-cell RNA sequencing (scRNA-seq) to profile human nasal mucosa obtained from the inferior turbinates, middle turbinates, and nasal polyps of CRSwNP patients, we identified two IL-1 signaling-induced cell subsets - LY6D+ club cells and IDO1+ fibroblasts - that promote neutrophil recruitment by respectively releasing S100A8/A9 and CXCL1/2/3/5/6/8 into inflammatory regions. IL-1beta, a pro-inflammatory cytokine involved in IL-1 signaling, induces the transdifferentiation of LY6D+ club cells and IDO1+ fibroblasts from primary epithelial cells and fibroblasts, respectively. In an LPS-induced neutrophilic CRSwNP mouse model, blocking IL-1beta activity with a receptor antagonist significantly reduced the numbers of LY6D+ club cells and IDO1+ fibroblasts and mitigated nasal inflammation. This study reveals the roles of two cell subsets in neutrophil recruitment and demonstrates an IL-1-based intervention for mitigating neutrophilic inflammation in CRSwNP.

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Section: Introductionmentioning

confidence: 96%

Transdifferentiation of epithelial cells and fibroblasts induced by IL-1β fuels neutrophil recruitment in chronic rhinosinusitis

Xie,

Wang,

Jin

et al. 2024

Preprint

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Endoscopic Extended Sinus Surgery for Patients with Severe Chronic Rhinosinusitis with Nasal Polyps, the Choice of Mucoplasty: A Systematic Review

Martin-Jimenez,

Moreno-Luna,

Cuvillo

et al. 2023

Curr Allergy Asthma Rep

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Purpose of Review The advances in the knowledge of the molecular basis of the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP) have led the management of these patients towards personalized and precision medicine. Surgery has been positioned as a suitable alternative in patients who do not achieve control with appropriate medical treatment, but polypoid recurrences remain a constraint. The emergence of new surgical approaches based on patient phenotyping and the poor disease control associated with type 2 inflammatory phenotype makes it necessary to review the role of personalized and precision surgery in managing the disease. Recent Findings Surgical approaches based on wide resection of bony sinus structures and the treatment of mucosa lining the sinonasal cavity have been analyzed and compared with other techniques and seem to offer more favorable surgical outcomes and improved quality of life (QoL), in addition to lower relapse rates. The innovations with new complementary surgical techniques, such as reboot surgery adding an extended autologous mucosal graft from the nasal floor (mucoplasty), may benefit endoscopic and QoL outcomes in the most severe CRSwNP patients with type 2 phenotype. Summary Using bilateral endonasal mucoplasty as a complementary technique to reboot surgery is a suitable technical choice that has improved short- and medium-term QoL and endoscopic outcomes for patients with severe CRSwNP. These results are likely due to a combination of the extension of reboot and the inherent inflammatory and healing properties of mucoplasty. We propose this technique as a valuable surgical resource, although more robust clinical studies are needed to evaluate its long-term benefits comprehensively.

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Association between interleukin-6-174G/C gene polymorphism and asthma severity: exploring the role of total serum IgE, blood eosinophils, and FeNO as markers of type 2 inflammation

Al-Ahmad,

Ali,

Maher

et al. 2024

Allergy Asthma Clin Immunol

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Background While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (− 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (− 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. Methods Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (− 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. Results In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 − 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001). Conclusion This study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (− 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

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Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps—A Systematic Review

Cited by 3 publications

References 122 publications

Transdifferentiation of epithelial cells and fibroblasts induced by IL-1β fuels neutrophil recruitment in chronic rhinosinusitis

Transdifferentiation of epithelial cells and fibroblasts induced by IL-1β fuels neutrophil recruitment in chronic rhinosinusitis

Endoscopic Extended Sinus Surgery for Patients with Severe Chronic Rhinosinusitis with Nasal Polyps, the Choice of Mucoplasty: A Systematic Review

Association between interleukin-6-174G/C gene polymorphism and asthma severity: exploring the role of total serum IgE, blood eosinophils, and FeNO as markers of type 2 inflammation

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