Allergic airway inflammation: key players beyond the Th2 cell pathway

Hirose, Koichi; Iwata, Arifumi; Tamachi, Tomohiro; Nakajima, Hiroshi

doi:10.1111/imr.12540

Cited by 113 publications

(71 citation statements)

References 232 publications

(494 reference statements)

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“…Their discovery led to the change in nomenclature from Th2-high asthma, which implied that these cytokines are exclusive products of Th2 cells, to type 2. Recent evidence also supports a role of ILC2s in the remodeling and repair of damaged tissue of asthma, disclosing new potential therapeutic target acting on the remodeling process [16]. …”

Section: Introductionmentioning

confidence: 99%

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Kuruvilla

Lee

2018

Clinic Rev Allerg Immunol

780

719

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The model of asthma as a single entity has now been replaced by a much more complex biological network of distinct and interrelating inflammatory pathways. The term asthma is now considered an umbrella diagnosis for several diseases with distinct mechanistic pathways (endotypes) and variable clinical presentations (phenotypes). The precise definition of these endotypes is central to asthma management due to inherent therapeutic and prognostic implications. This review presents the molecular mechanisms behind the heterogeneity of airway inflammation in asthmatic patients. Asthma endotypes may be broadly regarded as type 2 (T2) high or T2-low. Several biologic agents have been approved for T2-high asthma, with numerous other therapeutics that are incipient and similarly targeted at specific molecular mechanisms. Collectively, these advances have shifted existing paradigms in the approach to asthma to tailor novel therapies.

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Section: Introductionmentioning

confidence: 99%

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Kuruvilla

Lee

2018

Clinic Rev Allerg Immunol

780

719

View full text Add to dashboard Cite

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“…[2][3][4] Although a range of preventive and therapeutic strategies have been applied in the treatment of asthma, its prevalence has rapidly increased across the world, especially in children and young adults. 7,8 Gene expression studies of brushed bronchial epithelial cells in the lower airway have identified different asthmatic phenotypes based on observed expression profiles. 7,8 Gene expression studies of brushed bronchial epithelial cells in the lower airway have identified different asthmatic phenotypes based on observed expression profiles.…”

Section: Introductionmentioning

confidence: 99%

Identification of surrogate prognostic biomarkers for allergic asthma in nasal epithelial brushing samples by WGCNA

Liu

Fang

et al. 2018

J of Cellular Biochemistry

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Background Allergic asthma is a lower respiratory tract disease of Th2 inflammation with multiple molecular mechanisms. The upper and lower airways can be unified by the concept of a united airway and, as such, gene expression studies of upper epithelial cells may provide effective surrogate biomarkers for the prognostic study of allergic asthma. Objective To identify surrogate biomarkers in upper airway epithelial cells for the prognostic study of allergic asthma. Methods Nasal epithelial cell gene expression in 40 asthmatic and 17 healthy control subjects were analyzed by weighted gene coexpression network analysis (WGCNA) to identify gene network modules and profiles in allergic asthma. Functional enrichment analysis was performed on the coexpression genes in certain highlighted modules. Results A total of 13 coexpression modules were constructed by WGCNA from 2804 genes in nasal epithelial brushing samples of the 40 asthmatic and 17 healthy subjects. The number of genes in these modules ranged from 1086 (Turquoise module) to 45 (Salmon). Eight coexpression modules were found to be significantly correlated (P < 0.05) with two clinic traits, namely disease status, and severity. Four modules were positively correlated ( P < 0.05) with the traits and these, therefore, contained genes that are mostly overexpressed in asthma. Contrastingly, the four other modules were found to be negatively correlated with the clinic traits. Functional enrichment analysis of the positively correlated modules showed that one (Magenta) was mainly enriched in mast cell activation and degranulation; another (Pink) was largely involved in immune cell response; the third (Yellow) was predominantly enriched in transmembrane signal pathways; and the last (Blue) was mainly enriched in substructure components of the cells. The hub genes in the modules were KIT, KITLG, GATA2, CD44, PTPRC, and CFTR, and these were confirmed as having significantly higher expression in the nasal epithelial cells. Combining the six hub genes enabled a relatively high capacity for discrimination between asthmatics and healthy subjects with an area under the receiver operating characteristic (ROC) curve of 0.924. Conclusions Our findings provide a framework of coexpression gene modules from nasal epithelial brushing samples that could be used for the prognostic study of allergic asthma.

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“…Christianson et al demonstrated elevated IL‐33 and ILC2 levels in BAL of patients with asthma and IL‐33 correlated with disease severity. ILC2s from patients with severe asthma produce more IL‐5 and IL‐13 upon in vitro exposure to IL‐25, IL‐33, and TSLP than those from healthy controls, indicating their pre‐activated state in disease . The disease severity correlates with the level of ILC2 enrichment, as demonstrated by Bartemes et al .…”

Section: Ilc2s In Diseasementioning

confidence: 75%

New insights into the function, development, and plasticity of type 2 innate lymphoid cells

Krabbendam

Bal

Spits

et al. 2018

Immunological Reviews

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Summary Group 2 innate lymphoid cells (ILC2s) are the most well defined group of ILCs. ILC2 development is controlled by the GATA‐3 transcription factor and these cells produce archetypal type 2 cytokines, such as IL‐5 and IL‐13. These cytokines mediate parasite expulsion and tissue repair, but also contribute to type 2 inflammatory diseases, including allergy, asthma and chronic rhinosinusitis with nasal polyps. In response to tightly regulated local environmental cues ILCs can generate characteristics of other subtypes, a process known as plasticity. Recent advances in the ILC2 field has led to the discovery that ILC2s can promptly shift to functional IFN‐γ‐producing ILC1s or IL‐17‐producing ILC3s, depending on the cytokines and chemokines produced by antigen presenting cells or epithelial cells. Due to yet unknown triggers, this complex network of signals may become dysregulated. In this review, we will discuss general ILC characteristic, ILC2 development, plasticity, memory function, and implications in disease.

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Allergic airway inflammation: key players beyond the Th2 cell pathway

Cited by 113 publications

References 232 publications

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Identification of surrogate prognostic biomarkers for allergic asthma in nasal epithelial brushing samples by WGCNA

New insights into the function, development, and plasticity of type 2 innate lymphoid cells

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