The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis

Wang, Hai; Li, Zhi Yong; Jiang, Wen; Liao, Bo; Zhai, Guan Ting; Wang, Nan; Zhen, Zhen; Ruan, Jian; Long, Xiao; Wang, Heng; Liu, Wei Hong; Liang, Gengtian; Xu, Wei; Kato, Atsushi; Liu, Zheng

doi:10.1016/j.jaci.2017.12.972

Cited by 103 publications

(176 citation statements)

References 67 publications

(139 reference statements)

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“…27 Wang et al confirmed that both eosinophilic and noneosinophilic CRSwNP in Wuhan, China had elevated expression of IFN-γ and IL-17A compared with control, and noneosinophilic CRSwNP had even higher IFN-γ and IL-17A expression compared to eosinophilic CRSwNP. 34 Consistently, Shi et al and Ma et al found that Th1 and Th17 cell counts, as well as Tc1 and Tc17 cell counts, were increased in noneosinophilic CRSwNP versus eosinophilic CRSwNP and control in Chinese. 37,57 The number of ILC2s in noneosinophilic CRSwNP was comparable to that in healthy controls, but decreased as compared with that in eosinophilic CRSwNP.…”

Section: Immune Polarization In Crsmentioning

confidence: 73%

“…26 The recently published study by Wang et al demonstrated that increased production and activation of epithelial cell-derived IL-36γ may act on neutrophils and further amplify neutrophilic inflammation in CRS (Fig 2). 34 IL-17A was able to upregulate the expression of IL-36γ in nasal epithelial cells in vitro , which may further promote neutrophilic inflammation in CRS. 34 Neutrophils were found to produce TGF-β2 in sinonasal mucosa, which may be involved in fibrosis in CRSsNP and noneosinophilic CRSwNP.…”

Section: Immune Polarization In Crsmentioning

confidence: 91%

“…27,28,34 In Chinese, both eosinophilic and noneosinophilic CRSwNP had elevated number of neutrophils with higher number of neutrophils in noneosinophilic CRSwNP than in the eosinophilic type. 35,37,53 A study on patients in Chicago discovered that nasal polyps, which are highly eosinophilic, also have significant levels of neutrophils.…”

Section: Immune Polarization In Crsmentioning

confidence: 97%

“…33 Noneosinophilic CRSwNP commonly demonstrates type1/type 3 predominant immune responses. 34 Thus, when taken as a whole, Asian patients with CRSwNP have lower frequency of type 2 cytokine expression, less eosinophilic inflammation, and lower asthma comorbidity as compared with their Caucasian counterparts. 33 Regarding CRSsNP, although most studies reported that the majority of patients presented noneosinophilic inflammation, a variable percentage of patients with a type 2-skewed inflammation could also be noted.…”

Section: Immune Polarization In Crsmentioning

confidence: 99%

“…46,58 Neutrophil counts, and the levels of myeloperoxidase (MPO), IL-8 and IL-36 were higher in patients with CRSsNP than those in control subjects. 27,34 …”

Section: Immune Polarization In Crsmentioning

confidence: 99%

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Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Cao

Wang

Schleimer

et al. 2019

Annals of Allergy, Asthma & Immunology

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102

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Objective: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on the transcription factor expression and cytokine production patterns in different types of innate lymphoid cells (ILCs), in parallel with those of adaptive CD4+ T helper (Th) cells and CD8+ cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging around the immune response deviation into type 1 (orchestrated by ILC1s, Tc1 and Th1 cells), type 2 (characterized by ILC2s, Tc2 and Th2 cells), and type 3 (mediated by ILC3s, Tc17 and Th17 cells) responses. Additionally, cluster analysis has been applied to the endotyping of CRS in recent years, which has provided additional novel insights into the CRS pathogenesis. This article aims to review pathological mechanisms of CRS on the basis of type 1, type 2, and type 3 immune responses and how they inform us to begin to understand CRS endotypes. This article also reviews the recent cluster analysis studies of CRS endotypes. Finally, the impact of endotype on therapeutic management of CRS is summarized. Data Sources: Review of published literature. Study Selections: Relevant literature concerning CRS endotypes and the possible underlying mechanisms were obtained from a PubMed search and summarized here. Results and Conclusion: Both CRSwNP and CRSsNP are comprised of distinct endotypes with distinct deviated immune responses, pathogenic mechanisms, and different responses to medical and surgical treatment. An endotype of CRS with prominent type 2 immune responses is the most well studied endotype, and generally can benefit from treatment with steroids and specific type 2 disrupting biologics.

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Section: Immune Polarization In Crsmentioning

confidence: 73%

Section: Immune Polarization In Crsmentioning

confidence: 91%

Section: Immune Polarization In Crsmentioning

confidence: 97%

Section: Immune Polarization In Crsmentioning

confidence: 99%

“…46,58 Neutrophil counts, and the levels of myeloperoxidase (MPO), IL-8 and IL-36 were higher in patients with CRSsNP than those in control subjects. 27,34 …”

Section: Immune Polarization In Crsmentioning

confidence: 99%

See 3 more Smart Citations

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Cao

Wang

Schleimer

et al. 2019

Annals of Allergy, Asthma & Immunology

Self Cite

102

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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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Enhanced oxidative stress is associated with tissue neutrophilia and poor steroid response in chronic rhinosinusitis with nasal polyps

Chen

Cao

et al. 2023

World j. otorhinolaryngol.-head neck surg.

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ObjectiveTo analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients.MethodsThe levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA (mRNA) levels of superoxide dismutase 2 (SOD2), aldehyde dehydrogenase 1 (ALDH1A1), and microsomal glutathione S‐transferase 1 (MGST1) were examined using quantitative real‐time polymerase chain reaction in the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients.ResultsThe levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by the area under the curve.ConclusionThese findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

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The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis

Abstract: Increased production and activation of IL-36γ may act on neutrophils and further exaggerate neutrophilic inflammation in CRS.

Cited by 103 publications

References 67 publications

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

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

Enhanced oxidative stress is associated with tissue neutrophilia and poor steroid response in chronic rhinosinusitis with nasal polyps

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