Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Hekking, Pieter-Paul; Loza, Matthew J.; Pavlidis, Stelios; Meulder, Bertrand De; Lefaudeux, Diane; Baribaud, Fred; Auffray, Charles; Wagener, Ariane H.; Brinkman, Paul; Lutter, René; Bansal, Aruna T.; Sousa, Ana R.; Bates, Steve A.; Pandis, Yannis; Fleming, Louise; Shaw, Debra J.; Fowler, Stephen J.; Guo, Yike; Meiser, Andrea; Sun, Kai; Corfield, Julie; Howarth, Peter H.; Bel, Elisabeth H.; Adcock, Ian M.; Chung, Kian Fan; Djukanović, Ratko; Sterk, Peter J.

doi:10.1016/j.jaci.2017.06.037

Cited by 110 publications

(110 citation statements)

References 45 publications

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“…102 Indeed, NK cells have also been observed to exacerbate pathology during highdose influenza infection, 103 and may themselves be susceptible to influenza infection, causing reduced cytotoxicity and production of pro-inflammatory cytokines. CD56 + CD16 + NK cells isolated from the airways of COPD patients have increased natural cytotoxicity in comparison to those from controls, 93 and demonstrate increased killing of autologous lung cells in co-culture experiments. 98 Like ILC1s, lung NK cells may contribute to chronic inflammatory disorders, such as COPD and asthma through production of inflammatory cytokines.…”

Section: Ilc3smentioning

confidence: 96%

“…90 ILC3s can also drive inflammatory responses, as IL-17 + ILC3s mediate airway hyperresponsiveness in both obesity-linked asthma 91 and allergic asthma induced by house dust mite challenge. 93 NK cells NK cells are classified as members of the ILC1 family based on shared transcription factor requirements and IFN-c production, but perform important cytolytic functions through their secretion of perforin and granzyme B. 93 NK cells NK cells are classified as members of the ILC1 family based on shared transcription factor requirements and IFN-c production, but perform important cytolytic functions through their secretion of perforin and granzyme B.…”

Section: Ilc3smentioning

confidence: 99%

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Tissue‐resident innate immunity in the lung

2019

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The lung is a unique organ that must protect against inhaled pathogens and toxins, without mounting a disproportionate response against harmless particulate matter and without compromising its vital function. Tissue-resident immune cells within the lung provide local immunity and protection from infection but are also responsible for causing disease when dysregulated. There is a growing appreciation of the importance of tissue-resident memory T cells to lung immunity, but non-recirculating, tissue-resident, innate immune cells also exist. These cells provide the first line of defence against pulmonary infection and are essential for co-ordinating the subsequent adaptive response. In this review, we discuss the main lung-resident innate immune subsets and their functions in common pulmonary diseases, such as influenza, bacterial pneumonia, asthma and inflammatory disorders.

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Section: Ilc3smentioning

confidence: 96%

Section: Ilc3smentioning

confidence: 99%

Tissue‐resident innate immunity in the lung

2019

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“…Moreover, this approach avoids reliance on measures of mRNA which lack linear association with actual protein synthesized . Although several recent reports have examined gene expression patterns in sputum and bronchial epithelial samples from subjects with severe asthma, these have included more limited information on corresponding protein analyses . One report from U‐BIOPRED, examining protein differences between 4 clinically identified cluster groups, found 9 differentially abundant sputum proteins in more severe clusters compared to moderate, well‐controlled asthma with normal FEV1 .…”

Section: Introductionmentioning

confidence: 99%

“…23 Although several recent reports have examined gene expression patterns in sputum and bronchial epithelial samples from subjects with severe asthma, these have included more limited information on corresponding protein analyses. [24][25][26][27] One report from U-BIOPRED, examining protein differences between 4 clinically identified cluster groups, found 9 differentially abundant sputum proteins in more severe clusters compared to moderate, well-controlled asthma with normal FEV1. 28 However, the 1 cluster group with greatest number of differentially abundant proteins was characterized by 16-packyear smoking history which may influence and contribute to these elevated proteins.…”

Section: Introductionmentioning

confidence: 99%

Complex association patterns for inflammatory mediators in induced sputum from subjects with asthma

Hastie

Steele

Dunaway

et al. 2018

Clin Experimental Allergy

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Sputum cytokines, chemokines and growth factors were increased in severe asthma, primarily with increased neutrophils. Factor analysis identified complex inflammatory protein interactions, suggesting airway inflammation in asthma is characterized by overlapping immune pathways. Thus, focus on a single specific inflammatory mediator or pathway may limit understanding the complexity of inflammation underlying airway changes in asthma and selection of appropriate therapy.

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“…In contrast to genomics, epigenomics, and transcriptomics profiles are tissue-specific and in complex diseases such as asthma, several types of tissues and cells are involved in the disease pathology. 116,135 Hence, to gain a better understanding of the disease, samples from different tissues must be collected. Furthermore, epigenomic and transcriptomic profiles can be influenced by various factors such as time of tissue sampling, sampling technique, environmental factors, which can cause problems in large sample sizes, and longitudinal study design.…”

Section: Putting Omics Togethermentioning

confidence: 99%

The use of pharmacogenomics, epigenomics, and transcriptomics to improve childhood asthma management: Where do we stand?

Farzan

Vijverberg

Kabesch

et al. 2018

Pediatric Pulmonology

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Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals. However, biologicals are recommended only for patients with specific asthma phenotypes who remain uncontrolled despite high dosages of conventional asthma treatment. One of the main unmet needs in their application is lack of clinically available biomarkers to individualize pediatric asthma management and guide treatment. Pharmacogenomics, epigenomics, and transcriptomics are three omics fields that are rapidly advancing and can provide tools to identify novel asthma mechanisms and biomarkers to guide treatment. Pharmacogenomics focuses on variants in the DNA, epigenomics studies heritable changes that do not involve changes in the DNA sequence but lead to alteration of gene expression, and transcriptomics investigates gene expression by studying the complete set of mRNA transcripts in a cell or a population of cells. Advances in high-throughput technologies and statistical tools together with well-phenotyped patient inclusion and collaborations between different centers will expand our knowledge of underlying molecular mechanisms involved in disease onset and progress. Furthermore, it could help to select and stratify appropriate therapeutic strategies for subgroups of patients and hopefully bring precision medicine to daily practice.

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Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Abstract: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.

Cited by 110 publications

References 45 publications

Tissue‐resident innate immunity in the lung

Tissue‐resident innate immunity in the lung

Complex association patterns for inflammatory mediators in induced sputum from subjects with asthma

The use of pharmacogenomics, epigenomics, and transcriptomics to improve childhood asthma management: Where do we stand?

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