Asthma from immune pathogenesis to precision medicine

Khalaf, Kareem; Paoletti, Giovanni; Puggioni, Francesca; Racca, Francesca; Luca, Fabrizio De; Giorgis, Veronica; Canonica, Giorgio Walter; Heffler, Enrico

doi:10.1016/j.smim.2019.101294

Cited by 46 publications

(42 citation statements)

References 101 publications

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“…Asthma includes many clinical presentations with different types of excessive immunological responses [2,3] which involve many immune cells and broblasts and epithelial cells [26]. Activation of airway epithelial cells and release of cytokines including IL-25, IL-33, and TSLP play a major role in onset of asthma [27].…”

Section: Discussionmentioning

confidence: 99%

“…Asthma is one of the most common noninfectious chronic diseases, affecting more than 300 million people worldwide [1]. Asthma is characterized by various immunological mechanisms [2] and resulted from complex gene-environment interactions with heterogeneous clinical presentation [3]. The central theme of asthma is type 2-mediated allergic in ammatory responses that promote barrier defenses at mucosal surfaces [4].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis

Zhang¹,

Feng

Fan

et al. 2020

Preprint

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Background: Asthma is one of the most common noninfectious chronic diseases characterized by type II inflammation. This study aimed to investigate the effects of molecular hydrogen on the pathogenesis of asthma.Methods: OVA sensitized asthma mouse model was established and hydrogen/oxygen mixture was used to treat asthmatic mice. Serum and BALF cytokines were measured with specific ELISA assays. E-cadherin and ZO-1 were detected by immunohistochemical staining and expression of caspase 3 and 9, NF-kB, IL-33 and ST2 was assessed by quantitative real-time PCR, western blot and / or immunofluorescence. IL-33 promoter activity was analyzed by dual-luciferase assay. ILC2 population was assayed by flow cytometry and differentially expressed miRNAs were detected using miRNA array. Results: Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H2 in asthmatic mice. The expression of NF-kB (p65) and ST2 was upregulated by OVA and suppressed by H2. ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H2. E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H2 treatment. H2 alleviated HDM induced apoptosis of 16HBE cells, upregulation of IL-33 and ST2, and elevation of IL-33 promoter activity. A group of miRNAs differentially expressed in HDM and HDM+H2 treated 16HBE cells were identified. Conclusions: These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutic method for asthma and other conditions of type II inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis

Zhang¹,

Feng

Fan

et al. 2020

Preprint

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“…Type 2 immunity induces a complex response involving granulocytes (eosinophils, basophils), mastocytes, type 2-innate lymphoid cells (ILC2), IL-4-and/or IL-13conditioned macrophages and T helper 2 (Th2) cells [24]. These cells are crucial to the pathogenesis of CRS and related disorders (asthma [25]), therefore, driving mechanisms that control intensity, maintenance and resolution of type 2 immunity are reasonably important regulators of disease progression and have to be fully understood for therapeutical purposes.…”

Section: Immunological Mechanismsmentioning

confidence: 99%

Care about patients with chronic rhinosinusitis and type-2 inflammation

Pirola¹,

Heffler²,

Paoletti³

et al. 2020

Preprint

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“…Asthma is a very diffuse chronic respiratory disease whose main pathologic features include airway inflammation and remodelling, which are responsible for variable airflow limitation and bronchial hyperresponsiveness (1)(2)(3). More than 300 million people currently suffer from asthma worldwide, and this number is probably destined to undergo further increases during the next years (4,5).…”

Section: Introductionmentioning

confidence: 99%

Molecular Targets for Biological Therapies of Severe Asthma

et al. 2020

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Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). Within this context, during the last years several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. In addition to pro-allergic immunoglobulin E (IgE), that chronologically represents the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed, today other targets are successfully exploited by biological treatments of severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor. Moreover, dupilumab behaves as a dual receptor antagonist of pleiotropic interleukins 4 (IL-4) and 13 (IL-13). Besides these drugs that are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, also including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing the global scenario of severe asthma management. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, that are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. Such tailored strategies are thus allowing to successfully target the immune-inflammatory responses underlying uncontrolled T2-high asthma.

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Asthma from immune pathogenesis to precision medicine

Cited by 46 publications

References 101 publications

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis

Care about patients with chronic rhinosinusitis and type-2 inflammation

Molecular Targets for Biological Therapies of Severe Asthma

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Asthma from immune pathogenesis to precision medicine

Cited by 46 publications

References 101 publications

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2&nbsp;Axis

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2&nbsp;Axis

Care about patients with chronic rhinosinusitis and type-2 inflammation

Molecular Targets for Biological Therapies of Severe Asthma

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Product

Resources

About

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis