Interleukin-4 and interleukin-13 pathway genetics affect disease susceptibility, serum immunoglobulin E levels, and gene expression in asthma

Li, Jia; Lin, Lihui; Wang, Juan; Xia, Peng; Dai, Hui-Rong; Xiao, Hui; Li, Fēi; Wang, Yuping; Yang, Zhijun; Li, Li

doi:10.1016/j.anai.2014.05.004

Cited by 27 publications

(18 citation statements)

References 23 publications

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“…Asthma is commonly associated with enhanced STAT6 and Ige gene expression that are linked to an increase in HAT activities and decrease in HDAC activities (Gunawardhana et al, 2014;Li et al, 2014). Consistent with these studies, our data confirmed the association of hyperacetylation of histone H3 with asthma (Fig.…”

Section: Acetylation Of H3k9 Associated With Asthma In Il-4/stat6 Patsupporting

confidence: 81%

Histone H3k9 and H3k27 Acetylation Regulates IL‐4/STAT6‐Mediated Igε Transcription in B Lymphocytes

Wang

Duan

et al. 2015

The Anatomical Record

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IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Ige via chromatin remodeling involved in B lymphocytes development. STAT6 acts as a molecular switch to regulate the higher-order chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN) and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form a complex, balancing the acetylation and deacetylation states to co-regulate IL-4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment increased the HATs activity in Ramos cells. As "active" markers, the expression of H3K9ac and H3K27ac increased after treatment with IL-4. However, transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the Ige promoter regions. Our results revealed that the Ige gene transcription is regulated by histone modifications in the IL-4/STAT6 pathway. The study will provide novel insights into the pathogenesis of allergic diseases.

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Section: Acetylation Of H3k9 Associated With Asthma In Il-4/stat6 Patsupporting

confidence: 81%

Histone H3k9 and H3k27 Acetylation Regulates IL‐4/STAT6‐Mediated Igε Transcription in B Lymphocytes

Wang

Duan

et al. 2015

The Anatomical Record

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“…In agreement with our findings, Gene expression analysis of Li et al [38] showed that patients with 4 SNPs (rs2243250, rs1800925, rs1805010, and rs3224011) in STAT6 gene had higher expression levels of IL-4, IL-13, and STAT6. It has been also detected that in bronchial asthma the over expression of IL-4 occurs via the activation of the STAT6 pathway thus showing that STAT6 plays a positive role, affecting the expression of IL-4 [39].…”

Section: Discussionsupporting

confidence: 81%

Association of STAT6 rs324011 Gene Polymorphism with Susceptibility of Atopic Bronchial Asthma in Egyptian Children

El-Gohary¹,

Wagih²,

Hamouda³

et al. 2018

Biochem Mol biol J

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Background: Bronchial asthma is a common disease with multiple determinants that include genetic variation. Signal transducer and activator of transcription 6 (STAT6) is a central molecule in the signal transduction pathway used by interleukin-4 (IL-4) in immunoglobulin E (IgE) isotype switching. Study Objective was to investigate whether single nucleotide polymorphism (SNP) in STAT6 is associated with atopic asthma susceptibility in Egyptian children and to correlate the effect of STAT6 gene polymorphism on IL-4 and total IgE levels.

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“… 44,45 Furthermore, allergic patients who are predisposed to asthma might exhibit intrinsic features, such as epithelial barrier defects, increased atopic predisposition, or both, that render them more susceptible to allergic sensitization. 46,47 The net result of these mechanisms would be a more frequent and more intense IgE recognition of individual allergens present in a complex allergen source, such as HDM, which is preferentially associated with asthma, whereas sensitization to fewer allergens is more related to rhinitis. It has been suggested that children might acquire additional IgE sensitizations with increasing age, 24 and it is therefore possible that the fact that asthmatic children reacted with more HDM allergens could be due to a bias toward higher age in this group.…”

Section: Discussionmentioning

confidence: 99%

Different IgE recognition of mite allergen components in asthmatic and nonasthmatic children

Resch

Michel

Kabesch

et al. 2015

Journal of Allergy and Clinical Immunology

115

109

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BackgroundHouse dust mites (HDMs) represent one of the most important inducers of respiratory allergies worldwide.ObjectiveWe sought to investigate the IgE and IgG reactivity profiles to a comprehensive panel of HDM allergens in children with allergic asthma and to compare them with those of nonasthmatic atopic children.MethodsSera from clinically well-characterized asthmatic children with HDM allergy (n = 105), nonasthmatic children (n = 53), and nonatopic nonasthmatic children (n = 53) were analyzed for IgE and IgG reactivity to a panel of 7 HDM allergens (nDer p 1, rDer p 2, rDer p 5, rDer p 7, rDer p 10, rDer p 21, and rDer p 23) by means of allergen microarray technology.ResultsAsthmatic children with HDM allergy more frequently showed an IgE response to each of the HDM allergens and recognized more allergens than nonasthmatic children with HDM allergy. Furthermore, IgE levels to certain HDM allergens (nDer p 1, P = .002; rDer p 2, P = .007; rDer p 5, P = .031; and rDer p 23, P < .001) were significantly higher in asthmatic children than in children without asthma. By contrast, fewer asthmatic children showed IgG reactivity to HDM allergens than nonasthmatic children, but allergen-specific IgG levels were comparable.ConclusionThe IgE and IgG reactivity profiles to HDM allergens, as well as IgE levels to certain allergen components, differed considerably between children with and without asthmatic symptoms caused by HDM allergy. In fact, asthmatic children were characterized by an expanded IgE repertoire regarding the numbers of recognized allergen components and by increased specific IgE levels.

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Interleukin-4 and interleukin-13 pathway genetics affect disease susceptibility, serum immunoglobulin E levels, and gene expression in asthma

Cited by 27 publications

References 23 publications

Histone H3k9 and H3k27 Acetylation Regulates IL‐4/STAT6‐Mediated Igε Transcription in B Lymphocytes

Histone H3k9 and H3k27 Acetylation Regulates IL‐4/STAT6‐Mediated Igε Transcription in B Lymphocytes

Association of STAT6 rs324011 Gene Polymorphism with Susceptibility of Atopic Bronchial Asthma in Egyptian Children

Different IgE recognition of mite allergen components in asthmatic and nonasthmatic children

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