Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit

North, Michelle L.; Jones, Meaghan J.; MacIsaac, Julia L.; Morin, Alexander M.; Steacy, Lisa M.; Gregor, Alexander; Kobor, Michæl S.; Ellis, Anne K.

doi:10.1111/all.13263

Cited by 41 publications

(39 citation statements)

References 43 publications

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“…Instead some epigenetic modifications must be involved in the onset of AR (Shinohara et al, 2007 , TPSG1, SLFN12 and MUC4 in the peripheral blood mononuclear cells (North et al, 2018), and IL13 in house dust mite-sensitized AR patients (Li et al, 2016). However, this association did not occur with late pregnancy or with paternal AR symptoms, which clearly demonstrated this disease was not solely due to genetic information transferred from the parents.…”

Section: Discussionmentioning

confidence: 97%

“…Instead some epigenetic modifications must be involved in the onset of AR (Shinohara et al, 2007 (Nestor et al, 2014). Recently more and more case studies have revealed aberrant methylation status in the promoter regions of AR-related genes, such as IFNG and IL4 in CD4 + T cells of paediatric AR , TPSG1, SLFN12 and MUC4 in the peripheral blood mononuclear cells (North et al, 2018), and IL13 in house dust mite-sensitized AR patients (Li et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Two recent publications identified elevated DNA methylation level in the promoter regions of interferon (IFN)-and IL-4 in CD4 + T cells of pediatric AR (Li, Mu, Wang, Liu, & Jiang, 2018;Li, Rui, Ma, Jiang, & Chen, 2019), which was further revealed to be regulated via the extracellular signal-regulated kinase-DNA methyltransferase pathway as illustrated in the murine model (Li, Zhou, Rui, Zhou, & Mo, 2019). By comparing DNA methylation profiles in peripheral blood mononuclear cells before and after grass pollen exposure, 42 sites showing a significantly higher level of DNA methylation were discovered, among which three genes were further validated by pyrosequencing, namely TPSG1, SLFN12 and MUC4 (North et al, 2018). Hypomethylation of the IL13 gene was observed, in company with increase expression of IL-13 and serum IgE overloading, which in turn led to higher susceptibility to AR from house dust mite sensitization (Li et al, 2016).…”

Section: Introductionmentioning

confidence: 96%

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MiR‐199‐3p–Dnmt3a–STAT3 signalling pathway in ovalbumin‐induced allergic rhinitis

Cui

Guo

Wang

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?What is the mechanism of DNA methylation in allergic rhinitis? What is the main finding and its importance?A miR‐199‐3p–Dnmt3a–STAT3 signalling pathway is involved in ovalbumin‐induced allergic rhinitis, and miR‐199‐3p antagomir can relieve the symptoms in the mouse model. Abstract Recent research has pointed out the involvement of epigenetic modifications in allergic rhinitis (AR), especially DNA methylation. However, the detailed mechanism has remained largely uncovered. We used ovalbumin (OVA) to induce AR in mouse, and behaviour scores were used to confirm its successful establishment. Histamine and other inflammatory factors were detected to further verify success of the model. Real‐time PCR was employed to identify the overexpression of miR‐199‐3p and subsequent down‐regulation of DNA methyltransferase 3a (Dnmt3a). Western blotting was utilized to detect Dnmt3a and signal transducer and activator of transcription 3 (STAT3) at the protein level. Bisulfite sequencing PCR was applied to reveal the methylation status of the Stat3 promoter region. A dual‐reporter assay was used to confirm the direct targeting of miR‐199‐3p on the Dnmt3a mRNA and an antagomir specific to miR‐199‐3p was injected to rescue the symptoms of AR. The AR model was successfully established in mouse and confirmed by both behaviour and molecular markers. We also found lowered expression of Dnmt3a and consecutive hypomethylation of Stat3 promoter and elevated expression of STAT3, which then led to overexpression of IgE and other inflammatory factors. MicroRNAs that worked on the Dnmt3a 3′‐untranslated region were predicted and then verified by dual‐reporter assay. Finally injection of a miR‐199‐3p antagomir successfully attenuated the symptoms of AR. We propose that the miR‐199‐3p–Dnmt3a–STAT3 signalling pathway is involved in OVA‐induced AR.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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MiR‐199‐3p–Dnmt3a–STAT3 signalling pathway in ovalbumin‐induced allergic rhinitis

Cui

Guo

Wang

et al. 2019

Experimental Physiology

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“…These proteins instigate the adverse immune response in sensitized individuals (Figure 3) [128,154,155,156]. In addition, single and repeated exposures to pollen in allergic individuals have been shown to induce epigenetic changes, both in the blood and the nasal tissue [157]. …”

Section: Reviewmentioning

confidence: 99%

Aeroallergens in Canada: Distribution, Public Health Impacts, and Opportunities for Prevention

Sierra-Heredia

North

Brook

et al. 2018

IJERPH

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Aeroallergens occur naturally in the environment and are widely dispersed across Canada, yet their public health implications are not well-understood. This review intends to provide a scientific and public health-oriented perspective on aeroallergens in Canada: their distribution, health impacts, and new developments including the effects of climate change and the potential role of aeroallergens in the development of allergies and asthma. The review also describes anthropogenic effects on plant distribution and diversity, and how aeroallergens interact with other environmental elements, such as air pollution and weather events. Increased understanding of the relationships between aeroallergens and health will enhance our ability to provide accurate information, improve preventive measures and provide timely treatments for affected populations.

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“…In addition, changes in mucin 4 (MUC4) DNA methylation in nasal brushings correlate with decrease in peak nasal inspiratory flow. 22 Zhang et al 23 evaluated genome-wide DNA methylation patterns and allergic sensitization during adolescence and found that DNA methylation at cg10159529 is strongly correlated with expression of IL5RA, which is associated with allergic diseases. DNA methylation is considered to be strongly associated with allergic respiratory diseases.…”

mentioning

confidence: 99%

Recent developments and highlights in allergic rhinitis

Meng

Wang

Zhang

2019

Allergy

117

105

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Allergic rhinitis (AR) is a disease with high prevalence all over the world and therefore needs to be thoroughly investigated and treated accordingly. The mechanisms underlying the pathology and treatment of AR have been widely studied, but many aspects remain unclear and warrant further investigations. This review presents an overview of recently published papers highlighting the risk factors, mechanisms, and treatment of AR. Additionally, recent studies discussing the role of single nucleotide polymorphism, DNA methylation, regulatory B cells, group 2 innate lymphoid cells, immunotherapy, and biologics in AR are also covered. K E Y W O R D Sallergic rhinitis, biologics, epigenetics, risk factors, treatment | 2321 MENG Et al.

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Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit

Abstract: This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.

Cited by 41 publications

References 43 publications

MiR‐199‐3p–Dnmt3a–STAT3 signalling pathway in ovalbumin‐induced allergic rhinitis

MiR‐199‐3p–Dnmt3a–STAT3 signalling pathway in ovalbumin‐induced allergic rhinitis

Aeroallergens in Canada: Distribution, Public Health Impacts, and Opportunities for Prevention

Recent developments and highlights in allergic rhinitis

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