Eosinophils as Major Player in Type 2 Inflammation: Autoimmunity and Beyond

Folci, Marco; Ramponi, Giacomo; Arcari, Ivan; Zumbo, Aurora; Brunetta, Enrico

doi:10.1007/5584_2021_640

Cited by 22 publications

(16 citation statements)

References 180 publications

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“…( 28 ). Furthermore, the immune enrichment scores of eosinophils, monocytes, and neutrophils were also upregulated, which were involved in various autoimmune processes by several studies ( 31 – 33 ). In addition to biological processes related to autoimmunity, enrichment in pathways such as cell morphogenesis and differentiation were also observed in this subtype.…”

Section: Discussionmentioning

confidence: 88%

Identifying and validating molecular subtypes of biliary atresia using multiple high-throughput data integration analysis

Wang

Shen²,

Zhao³

et al. 2023

Front. Immunol.

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BackgroundBiliary atresia (BA) is the most common form of severe neonatal obstructive jaundice. The etiology and pathogenesis of BA are multifactorial, and different factors may interact to produce heterogeneous pathological features and clinical outcomes. Despite different pathological features, all patients received the same treatment strategy. This study performed integrative clustering analysis based on multiple high-throughput datasets to identify the molecular subtypes of BA and provide a new treatment strategy for personalized treatment of the different subtypes of BA.MethodsThe RNA sequence dataset GSE122340 in the Gene Expression Omnibus (GEO) database was downloaded; 31 BA and 20 control normal liver tissues were collected at our center for transcriptome sequencing, and clinical and follow-up data of BA patients were available. Molecular subtypes were identified using integrated unsupervised cluster analysis involving gene expression, biliary fibrosis, and immune enrichment scores based on the transcriptome dataset, and the results were validated using independent datasets.ResultsBased on the results of the integrated unsupervised clustering analysis, four molecular subtypes were identified: autoimmune, inflammatory, virus infection-related, and oxidative stress. The autoimmune subtype with a moderate prognosis was dominated by autoimmune responses and morphogenesis, such as the Fc-gamma receptor and Wnt signaling pathway. The biological process of the inflammatory subtype was mainly the inflammatory response, with the best prognosis, youngest age at surgery, and lowest liver stiffness. The virus infection-related subtype had the worst prognosis and was enriched for a variety of biological processes such as viral infection, immunity, anatomical morphogenesis, and epithelial mesenchymal transition. The oxidative stress subtype was characterized by the activation of oxidative stress and various metabolic pathways and had a poor prognosis. The above results were verified independently in the validation sets.ConclusionsThis study identified four molecular subtypes of BA with distinct prognosis and biological processes. According to the pathological characteristics of the different subtypes, individualized perioperative and preoperative treatment may be a new strategy to improve the prognosis of BA.

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Section: Discussionmentioning

confidence: 88%

Identifying and validating molecular subtypes of biliary atresia using multiple high-throughput data integration analysis

Wang

Shen²,

Zhao³

et al. 2023

Front. Immunol.

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“…Previous studies showed that elevated NOS2 expressions could enhance the release of NO, which was closely involved in vasodilation, microvascular leakage, smooth muscle relaxation, and abnormal glandular secretion [ 31 ]. As a common upper airway inflammatory disease, AR is typically characterized by a predominant Th2 response and eosinophil infiltration in nasal mucosa [ 32 – 34 ]. NO was proven to be pivotal in modulating the production of Th2 cytokines which were responsible for the migration of eosinophils into the airway mucosa [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of Nasal Nitric Oxide and Serum NOS2 Levels in the Efficacy of Subcutaneous Immunotherapy in Pediatric Patients with Allergic Rhinitis

Wen

Cheng

Xie

et al. 2022

Mediators of Inflammation

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Background. Subcutaneous immunotherapy (SCIT) is an effective therapy for allergic rhinitis (AR), but some AR patients still do not benefit from it. Nasal nitric oxide (nNO) and inducible nitric oxide synthase (iNOS/NOS2) act important roles in AR. This study aims to explore the abilities of serum NOS2 and nNO in predicting the clinical efficacy of SCIT in AR patients. Methods. We recruited 40 healthy controls (HCs) and 120 AR patients in this study. Serum NOS2 and nNO levels were compared between the two groups. In the AR group, patients underwent and finished 1-year of SCIT, and divided into the effective and ineffective groups, and the relationships between serum NOS2 and nNO levels and efficacy of SCIT were evaluated. Results. The serum NOS2 and nNO levels were higher in AR patients than HCs. In the effective group, the serum NOS2 and nNO levels were increased than the ineffective group. ROC curves presented that a combination of serum NOS2 and nNO exhibited promising predictive ability in predicting the clinical efficacy of SCIT. Conclusions. Serum NOS2 and nNO levels were enhanced in AR patients and might affect the efficacy of SCIT. The combined use of serum NOS2 and nNO levels could be a reliable and useful method for predicting the clinical efficacy of SCIT.

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“…Finally, the upregulation of eotaxin-3 (CCL26), secreted by tissue-resident cells, promotes eosinophil tissue infiltration [8]. Once in the tissues, eosinophils exert their cytotoxic activity by releasing granule proteins causing direct cellular damage and inflammation [9]. Activated eosinophils also produce IL-25, enhancing Th2 activity and contributing to the maintenance of a vicious inflammatory cycle [10].…”

Section: Eosinophilic Granulomatosis With Polyangiitis Pathophysiologymentioning

confidence: 99%

Biologics for eosinophilic granulomatosis with polyangiitis

Caminati

Maule

Bello

et al. 2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewThe link between severe asthma and eosinophilic granulomatosis with polyangiitis (EGPA) in terms of pathophysiological background, clinical manifestations and disease evolution has leaded to investigate the relevance of anti T2 monoclonal antibodies licensed for severe asthma patients as a treatment option for EGPA. The present review aimed to provide un update on EGPA pathophysiology and to critically summarize the most robust evidence coming from trials and real-life setting on the use of anti T2 biologics in EGPA patients.Recent findingsMepolizumab, an anti-interleukin-5 monoclonal antibody, is the only biologic drug targeting eosinophilic inflammation currently approved for EGPA treatment at the dose of 300 mg/4 weeks. Its use is restricted by the American College of Rheumatology guidelines to specific diseases phases and severity grades. However the most appropriate mepolizumab positioning and dose is still under investigation in the real life practice, which is providing an increasing amount of evidence confirming its efficacy, alone or in combination with other options in different disease stages. The relevance of other monoclonal antibodies interfering with T2 inflammation, including omalizumab and benralizumab, is under investigation but the evidence is still scarceSummaryTaking into account the suboptimal medium-long term safety profile of conventional EGPA treatments, the opportunity of selectively targeting eosinophilic inflammation certainly represents a revolutionary approach. However, further real-word evidence is required to effectively position the new treatments in the light of the disease complexity, including different immunological drivers, and individual variability.

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Eosinophils as Major Player in Type 2 Inflammation: Autoimmunity and Beyond

Cited by 22 publications

References 180 publications

Identifying and validating molecular subtypes of biliary atresia using multiple high-throughput data integration analysis

Identifying and validating molecular subtypes of biliary atresia using multiple high-throughput data integration analysis

Predictive Value of Nasal Nitric Oxide and Serum NOS2 Levels in the Efficacy of Subcutaneous Immunotherapy in Pediatric Patients with Allergic Rhinitis

Biologics for eosinophilic granulomatosis with polyangiitis

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