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1.
Int J Mol Sci ; 22(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34576307

RESUMO

In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.90); 10 non-obese, non-atopic asthmatic adults with normal BMI (23.88 ± 2.73); and 10 healthy controls with normal BMI (23.62 ± 3.74). All asthmatic patients were considered to represent a low type-2 asthma phenotype according to selective clinical parameters. RNA sequencing (RNA-Seq) was conducted on peripheral blood CD4+ T cells. Thousands of differentially expressed genes were identified in both asthma groups compared with heathy controls. The expression of interferon (IFN)-stimulated genes associated with IFN-related signaling pathways was specifically affected in obese asthmatics, while the gap junction and G protein-coupled receptor (GPCR) ligand binding pathways were enriched in both asthma groups. Furthermore, obesity gene markers were also upregulated in CD4+ T cells from obese asthmatics compared with the two other groups. Additionally, the enriched genes of the three abovementioned pathways showed a unique correlation pattern with various laboratory and clinical parameters. The specific activation of IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in the development of new stratified therapeutic approaches.


Assuntos
Asma/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Interferons/metabolismo , Obesidade/metabolismo , Transdução de Sinais , Adulto , Asma/complicações , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Receptores Acoplados a Proteínas G/metabolismo
2.
Microorganisms ; 9(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207425

RESUMO

Little is known about the interplay and contribution of oral microorganisms to allergic diseases, especially in children. The aim of the clinical study was to associate saliva and dental biofilm microbiome with allergic disease, in particular with allergic asthma. In a single-center study, allergic/asthmatic children (n = 15; AA-Chd; age 10.7 ± 2.9), atopic/allergic children (n = 16; AT/AL-Chd; 11.3 ± 2.9), and healthy controls (n = 15; CON-Chd; age 9.9 ± 2.2) were recruited. After removing adhering biofilms from teeth and collecting saliva, microbiome was analyzed by using a 16s-rRNA gene-based next-generation sequencing in these two mediums. Microbiome structure differed significantly between saliva and dental biofilms (ß-diversity). Within the groups, the dental biofilm microbiome of AA-Chd and AT/AL-Chd showed a similar microbial fingerprint characterized by only a small number of taxa that were enriched or depleted (4) compared to the CON-Chd, while both diseased groups showed a stronger microbial shift compared to CON-Chd, revealing 14 taxa in AA-Chd and 15 taxa in AT/AL-Chd that were different. This could be the first note to the contribution of dental biofilm and its metabolic activity to allergic health or disease.

3.
Nutrients ; 11(8)2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349704

RESUMO

Epidemiological studies identified raw cow's milk consumption as an important environmental exposure that prevents allergic diseases. In the present study, we investigated whether raw cow's milk has the capacity to induce tolerance to an unrelated, non-milk, food allergen. Histone acetylation of T cell genes was investigated to assess potential epigenetic regulation. Female C3H/HeOuJ mice were sensitized and challenged to ovalbumin. Prior to sensitization, the mice were treated with raw milk, processed milk, or phosphate-buffered saline for eight days. Allergic symptoms were assessed after challenge and histone modifications in T cell-related genes of splenocyte-derived CD4+ T cells and the mesenteric lymph nodes were analyzed after milk exposure and after challenge. Unlike processed milk, raw milk decreased allergic symptoms. After raw milk exposure, histone acetylation of Th1-, Th2-, and regulatory T cell-related genes of splenocyte-derived CD4+ T cells was higher than after processed milk exposure. After allergy induction, this general immune stimulation was resolved and histone acetylation of Th2 genes was lower when compared to processed milk. Raw milk reduces allergic symptoms to an unrelated, non-milk, food allergen in a murine model for food allergy. The activation of T cell-related genes could be responsible for the observed tolerance induction, which suggested that epigenetic modifications contribute to the allergy-protective effect of raw milk.


Assuntos
Montagem e Desmontagem da Cromatina , Epigênese Genética , Hipersensibilidade Alimentar/dietoterapia , Histonas/metabolismo , Tolerância Imunológica , Ativação Linfocitária , Leite/imunologia , Subpopulações de Linfócitos T/metabolismo , Acetilação , Animais , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Camundongos Endogâmicos C3H , Ovalbumina , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
4.
Epigenomics ; 9(4): 539-571, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28322581

RESUMO

Allergic diseases are on the rise in the Western world and well-known allergy-protecting and -driving factors such as microbial and dietary exposure, pollution and smoking mediate their influence through alterations of the epigenetic landscape. Here, we review key facts on the involvement of epigenetic modifications in allergic diseases and summarize and critically evaluate the lessons learned from epigenome-wide association studies. We show the potential of epigenetic changes for various clinical applications: as diagnostic tools, to assess tolerance following immunotherapy or possibly predict the success of therapy at an early time point. Furthermore, new technological advances such as epigenome editing and DNAzymes will allow targeted alterations of the epigenome in the future and provide novel therapeutic tools.


Assuntos
Epigenômica/métodos , Predisposição Genética para Doença , Hipersensibilidade/diagnóstico , Hipersensibilidade/genética , Epigênese Genética , Edição de Genes , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Humanos , Hipersensibilidade/tratamento farmacológico , Imunoterapia
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