IL-10 family cytokines in chronic rhinosinusitis with nasal polyps: From experiments to the clinic

Xuan, Lijia; Zhang, Nan; Wang, Xiangdong; Zhang, Luo; Bachert, Claus

doi:10.3389/fimmu.2022.947983

Cited by 12 publications

(10 citation statements)

References 93 publications

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“…IL-10R is the receptor of IL-10. IL-10, a typical Th2 cytokine, is capable of regulating M2 macrophages polarization and plays an essential role in regulating inflammatory responses of CRSwNP ( 46 ). However, a recent study indicated that the IL-10 production ability of M2 macrophages was impaired in ECRSwNP, though the number of M2 macrophages was increased ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps

et al. 2022

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BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the infiltration of macrophages especially M2 macrophages play pivotal roles in the pathogenesis of CRSwNP, but the underlying mechanisms remain undetermined. This study sought to identify potential biomarkers related to M2 macrophages in CRSwNP.MethodsThe expression datasets of GSE136825 and GSE179265 were download from Gene Expression Omnibus (GEO) database and merged. Then, CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were applied to identify M2 macrophage-related gene modules. Thereafter, differentially expressed genes (DEGs) related to M2 macrophages were selected to perform functional enrichment analyses. A protein-protein interaction (PPI) network was built to identify hub genes and quantitative real-time reverse transcriptions PCR was used to verify the bioinformatics results.ResultsA total of 92 DEGs associated with M2 macrophages were identified for further analysis. The results of Gene ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) analyses illustrated that M2 macrophage-associated DEGs primarily enriched in immune responses and extracellular matrix structure. PPI network analysis identified 18 hub genes related to M2 macrophages that might be pivotal in the pathogenesis of CRSwNP. After verification, AIF1, C1QA, C1QB, C3AR1, CCR1, CD163, CD4, CD53, CD86, CSF1R, CYBB, FCER1G, FCGR3A, IL10RA, ITGB2, LAPTM5, PLEK, TYROBP were identified as potential M2 macrophage-related biomarkers for CRSwNP.ConclusionThese findings yield new insights into the hub genes and mechanisms related to M2 macrophages in the pathogenesis of CRSwNP. Further studies of these hub genes would help better understand the disease progression and identify potential treatment targets.

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Section: Discussionmentioning

confidence: 99%

M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps

et al. 2022

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“…IL‐10 level was lower in patients with CRSwNP and CRSsNP than that in healthy controls, 99 while another study showed no significant difference in IL‐10 level in nasal mucosal tissue between CRSwNP and control subjects 100 . Since these studies involved the patients from different regions, Xuan et al 101 . attributed the difference in these findings to immunologic heterogeneity of CRS patients in different regions.…”

Section: Characteristics Of Mucin Hypersecretion In Different Endotyp...mentioning

confidence: 99%

“…97,98 IL-10 level was lower in patients with CRSwNP and CRSsNP than that in healthy controls, 99 while another study showed no significant difference in IL-10 level in nasal mucosal tissue between CRSwNP and control subjects. 100 Since these studies involved the patients from different regions, Xuan et al 101 attributed the difference in these findings to immunologic heterogeneity of CRS patients in different regions. IL-10 prevents protein misfolding via STAT1 and STAT3 signal transduction pathways, and thereby maintains mucin production in goblet cells and integrity of the mucus barrier (Figure 2).…”

Section: Il-10 and Mucinmentioning

confidence: 99%

Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis

Zhai,

Shao,

et al. 2024

Clinical & Translational All

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BackgroundChronic rhinosinusitis (CRS) is usually accompanied by mucin hypersecretion that can lead to mucus accumulation and impair nasal mucociliary clearance, thus exacerbating airway inflammation. Abnormal mucin hypersecretion is regulated by different T helper (Th) cytokines, which are associated with different endotype‐driven inflammatory responses. Therefore, it is of great significance to understand how these factors regulate mucin hypersecretion to provide precise treatment strategies for different endotypes of CRS.BodyThus far, the most common endotypes of CRS are classified as type 1, type 2, or type 3 immune responses based on innate and adaptive cell‐mediated effector immunity, and the representative Th cytokines in these immune responses, such as IFN‐γ, TNF‐α, IL‐4, IL‐5, IL‐13, IL‐10, IL‐17, and IL‐22, play an important regulatory role in mucin secretion. We reviewed all the related literature in the PubMed database to determine the expression of these Th cytokines in CRS and the role they play in the regulation of mucin secretion.ConclusionWe believe that the main Th cytokines involved in specific endotypes of CRS play a key role in regulating abnormal mucin secretion, which contributes to better understanding of the pathogenesis of CRS and provides therapeutic targets for airway inflammatory diseases associated with mucin hypersecretion.

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“…M2a macrophage also releases IL‐10, CCL22, and CCL17, which promote the infiltration of Th2 cells. The combination of IL‐10 and IL‐4 enhances the expression of M2a‐related genes in bone marrow‐derived macrophages, and increases eosinophil migration [81]. Additionally, IL‐13 stimulates the expression of low‐affinity IgE receptors CD23, MHC‐II, and phagocytic mannose receptors in monocytes of patients with asthma, thereby facilitating inflammatory responses [82].…”

Section: Il‐4/il‐13 Pathway In Nasal Type 2 Inflammationmentioning

confidence: 99%

IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy

Zhu,

Zhao,

Wang

2024

Eye & ENT Research

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Type 2 dominant inflammation in nasal mucosa is the key underlying pathophysiological mechanism of allergic rhinitis (AR) and most presentations of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin‐4 (IL‐4) and IL‐13 share common receptor subunits and signaling molecules, which lead to various pathological changes in different cells, playing key roles in the pathogenesis of nasal type 2 inflammation. Numerous clinical trials have shown that biologics targeting key molecules of the IL‐4/IL‐13 pathway, especially IL‐4 receptor alpha, can treat CRSwNP and AR with high efficacy, and are generally well tolerated. Several biologics have been approved for the treatment of difficult‐to‐control CRSwNP, while others also show promising results. Here, we review the IL‐4/IL‐13 pathway, its role in nasal type 2 inflammation, and current targeted therapies related to the IL‐4/IL‐13 pathway, with a focus on AR and CRSwNP.

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IL-10 family cytokines in chronic rhinosinusitis with nasal polyps: From experiments to the clinic

Cited by 12 publications

References 93 publications

M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps

M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps

Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis

IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy

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