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1.
Int Arch Allergy Immunol ; 180(4): 235-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31694044

RESUMO

Over the last decades, an increasing appearance of allergies and atopic disorders, such as asthma, dermatitis, and rhinitis, has been observed. The mechanisms of these disorders remain unclear, and therefore the development of novel therapies is limited. Current treatments are often symptomatic, nonspecific, or may have severe side effects. Further insights into the mechanisms of the underlying disease pathogenesis could reveal novel targets for treatment. In this review, we provide an update on recent basic and translational studies that offer novel insights and opportunities for the treatment of patients with atopic disorders.


Assuntos
Asma/etiologia , Dermatite Atópica/etiologia , Hipersensibilidade Alimentar/etiologia , Rinite Alérgica/etiologia , Alérgenos/imunologia , Asma/genética , Asma/terapia , Dermatite Atópica/genética , Dermatite Atópica/terapia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/terapia , Predisposição Genética para Doença/genética , Humanos , Rinite Alérgica/genética , Rinite Alérgica/terapia , Fatores de Risco
2.
J Sci Food Agric ; 99(15): 7008-7015, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31435932

RESUMO

BACKGROUND: Silkworm droppings have long been used in traditional medicine to remedy allergic itching, palsy, blood circulation problems, and arthritis in Asian countries. To investigate the anti-allergic effect of silkworm dropping extract (SDE) and its mechanism, we used a mouse model of food allergy induced by ovalbumin (OVA). RESULTS: SDE ameliorated the symptoms of OVA-induced food allergies, and the levels of T helper 2 (Th2)-related cytokines [such as interleukin (IL)-4, IL-5, IL-10, and IL-13] were found to be significantly decreased in both the spleen and mesenteric lymph nodes by SDE. Furthermore, SDE treatment directly inhibited OVA permeation, IL-4 production, and degranulation of mast cells; in contrast, immunoglobulin E (IgE) production from B cells was not affected. CONCLUSION: These results suggest that SDE has potential anti-allergic activities, and SDE may be useful in the treatment/prevention of allergic disorders such as food allergies, serving as therapeutic agents. © 2019 Society of Chemical Industry.


Assuntos
Antialérgicos/administração & dosagem , Bombyx/química , Fezes/química , Hipersensibilidade Alimentar/tratamento farmacológico , Células Th2/efeitos dos fármacos , Animais , Antialérgicos/química , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Células Th2/imunologia
3.
Nutrients ; 11(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284450

RESUMO

This review discusses the personalised dietary approach with respect to inflammatory bowel disease (IBD). It identifies gene-nutrient interactions associated with the nutritional deficiencies that people with IBD commonly experience, and the role of the Western diet in influencing these. It also discusses food intolerances and how particular genotypes can affect these. It is well established that with respect to food there is no "one size fits all" diet for those with IBD. Gene-nutrient interactions may help explain this variability in response to food that is associated with IBD. Nutrigenomic research, which examines the effects of food and its constituents on gene expression, shows that-like a number of pharmaceutical products-food can have beneficial effects or have adverse (side) effects depending on a person's genotype. Pharmacogenetic research is identifying gene variants with adverse reactions to drugs, and this is modifying clinical practice and allowing individualised treatment. Nutrigenomic research could enable individualised treatment in persons with IBD and enable more accurate tailoring of food intake, to avoid exacerbating malnutrition and to counter some of the adverse effects of the Western diet. It may also help to establish the dietary pattern that is most protective against IBD.


Assuntos
Deficiências Nutricionais/dietoterapia , Dieta Ocidental/efeitos adversos , Hipersensibilidade Alimentar/dietoterapia , Doenças Inflamatórias Intestinais/dietoterapia , Nutrigenômica/métodos , Estado Nutricional , Medicina de Precisão/métodos , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Adulto , Animais , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/genética , Deficiências Nutricionais/fisiopatologia , Comportamento Alimentar , Feminino , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/fisiopatologia , Interação Gene-Ambiente , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional/genética , Valor Nutritivo , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
4.
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
5.
PLoS One ; 14(6): e0218253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216310

RESUMO

BACKGROUND: Current laboratory tests are less than 50% accurate in distinguishing between people who have food allergies (FA) and those who are merely sensitized to foods, resulting in the use of expensive and potentially dangerous Oral Food Challenges. This study presents a purely-computational machine learning approach, conducted using DNA Methylation (DNAm) data, to accurately diagnose food allergies and potentially find epigenetic targets for the disease. METHODS AND RESULTS: An unbiased feature-selection pipeline was created that narrowed down 405,000+ potential CpG biomarkers to 18. Machine-learning models that utilized subsets of this 18-feature aggregate achieved perfect classification accuracy on completely hidden test cohorts (on an 8-fold hidden dataset). Ensemble classification was also shown to be effective for this High Dimension Low Sample Size (HDLSS) DNA methylation dataset. The efficacy of these machine learning classifiers and the 18 CpGs was further validated by their high accuracy on a large number of hidden data permutations, where the samples in the training, cross-validation, and hidden sets were repeatedly randomly allocated. The 18-CpG signature mapped to 13 genes, on which biological insights were collected. Notably, many of the FA-discriminating genes found in this study were strongly associated with the immune system, and seven of the 13 genes were previously associated with FA. CONCLUSIONS: Previous studies have also created highly-accurate classifiers for this dataset, using both data-driven and a priori biological insights to construct a 96-CpG signature. This research builds on previous work because it uses a completely computational approach to obtain a perfect classification accuracy while using only 18 highly discriminating CpGs (0.005% of the total available features). In machine learning, simpler models, as used in this study, are generally preferred over more complex ones (other things being equal). Lastly, the completely data-driven methodology presented in this research eliminates the need for a priori biological information and allows for generalizability to other DNAm classification problems.


Assuntos
Biomarcadores/sangue , Metilação de DNA/genética , Hipersensibilidade a Ovo/sangue , Hipersensibilidade Alimentar/sangue , Arachis/efeitos adversos , Epigênese Genética/genética , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/patologia , Humanos , Lactente , Recém-Nascido , Aprendizado de Máquina , Masculino
6.
Biomed Res Int ; 2019: 1315257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111043

RESUMO

Prenatal environmental exposures are considered to contribute to the development of allergic sensitization by epigenetic mechanisms. The role of histone acetylation in the placenta has not been examined yet. We hypothesized that placental histone acetylation at the promoter regions of allergy-related immune regulatory genes is associated with the development of sensitization to allergens in the child. Histones H3 and H4 acetylation at the promoter regions of 6 selected allergy-related immune regulatory genes was assessed by a chromatin immunoprecipitation assay in 173 term placentas collected in the prospective birth-cohort ALADDIN. The development of IgE sensitization to allergens in the children was followed from 6 months up to 5 years of age. We discovered significant associations of histone acetylation levels with decreased risk of allergic sensitization in 3 genes. Decreased risk of sensitization to food allergens was associated with higher H3 acetylation levels in placentas at the IFNG and SH2B3 genes, and for H4 acetylation in HDAC4. Higher HDAC4 H4 acetylation levels were also associated with a decreased risk of sensitization to aeroallergens. In conclusion, our results suggest that acetylation of histones in placenta has a potential to predict the development of sensitization to allergens in children.


Assuntos
Hipersensibilidade Alimentar/genética , Histona Desacetilases/genética , Interferon gama/genética , Proteínas/genética , Proteínas Repressoras/genética , Acetilação , Alérgenos/efeitos adversos , Pré-Escolar , Cromatina/genética , Epigênese Genética/genética , Epigênese Genética/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/patologia , Histona Desacetilases/imunologia , Histonas/genética , Histonas/imunologia , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Interferon gama/imunologia , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Placenta/imunologia , Placenta/patologia , Gravidez , Regiões Promotoras Genéticas/genética , Proteínas/imunologia , Proteínas Repressoras/imunologia
7.
Allergol. immunopatol ; 47(2): 152-158, mar.-abr. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-180803

RESUMO

Introduction and objectives: Long-term follow up of patients with hyper IgE syndrome (HIES), as a primary immunodeficiency disorder, has been poorly investigated. This study describes common clinical and immunological features of patients with HIES in the last 10 years in Shiraz University of Medical Sciences, Shiraz, Iran. Methods and patients: In this cross-sectional study, the symptoms and medical records of 18 patients, who were diagnosed with HIES, were observed. Genetic and immunologic study was also performed. Results: Eighteen patients with the mean age of 13 years old were investigated. Ten patients were detected to have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES). So, 14 patients with known genetic results were considered for further data analysis. Food allergy, eczema, viral and skin infections were the major complications of AR-HIES patients. The major clinical complications of AD-HIES patients were pneumonia, skin infections and eczema. Food allergy and viral infection were significantly higher in DOCK8 deficient patients. The most common causes of hospitalization in both AR-HIES and AD-HIES patients were pneumonia, skin infections and sepsis. The most common cause of death was found to be sepsis. Conclusions; AD-HIES and AR-HIES cannot be differentiated only based on the clinical presentations. Genetic features are also necessary for better diagnosis. This study, summarizing the clinical, immunological and genetic information of the patients with AD-HIES and AR-HIES, may open a way for better diagnosis and management of HIES


No disponible


Assuntos
Humanos , Masculino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Hipersensibilidade Alimentar/imunologia , Síndrome de Job/imunologia , Mutação/genética , Pneumonia/imunologia , Seguimentos , Hipersensibilidade Alimentar/genética , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/genética , Síndrome de Job/genética , Fenótipo , Pneumonia/genética , Fator de Transcrição STAT3/genética
8.
PLoS Comput Biol ; 15(2): e1006693, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30716085

RESUMO

Food allergy is usually difficult to diagnose in early life, and the inability to diagnose patients with atopic diseases at an early age may lead to severe complications. Numerous studies have suggested an association between the infant gut microbiome and development of allergy. In this work, we investigated the capacity of Long Short-Term Memory (LSTM) networks to predict food allergies in early life (0-3 years) from subjects' longitudinal gut microbiome profiles. Using the DIABIMMUNE dataset, we show an increase in predictive power using our model compared to Hidden Markov Model, Multi-Layer Perceptron Neural Network, Support Vector Machine, Random Forest, and LASSO regression. We further evaluated whether the training of LSTM networks benefits from reduced representations of microbial features. We considered sparse autoencoder for extraction of potential latent representations in addition to standard feature selection procedures based on Minimum Redundancy Maximum Relevance (mRMR) and variance prior to the training of LSTM networks. The comprehensive evaluation reveals that LSTM networks with the mRMR selected features achieve significantly better performance compared to the other tested machine learning models.


Assuntos
Classificação/métodos , Previsões/métodos , Hipersensibilidade Alimentar/genética , Humanos , Estudos Longitudinais , Aprendizado de Máquina , Memória de Longo Prazo/fisiologia , Memória de Curto Prazo/fisiologia , Microbiota , Máquina de Vetores de Suporte
9.
Allergol Immunopathol (Madr) ; 47(2): 152-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30279075

RESUMO

INTRODUCTION AND OBJECTIVES: Long-term follow up of patients with hyper IgE syndrome (HIES), as a primary immunodeficiency disorder, has been poorly investigated. This study describes common clinical and immunological features of patients with HIES in the last 10 years in Shiraz University of Medical Sciences, Shiraz, Iran. METHODS AND PATIENTS: In this cross-sectional study, the symptoms and medical records of 18 patients, who were diagnosed with HIES, were observed. Genetic and immunologic study was also performed. RESULTS: Eighteen patients with the mean age of 13 years old were investigated. Ten patients were detected to have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES). So, 14 patients with known genetic results were considered for further data analysis. Food allergy, eczema, viral and skin infections were the major complications of AR-HIES patients. The major clinical complications of AD-HIES patients were pneumonia, skin infections and eczema. Food allergy and viral infection were significantly higher in DOCK8 deficient patients. The most common causes of hospitalization in both AR-HIES and AD-HIES patients were pneumonia, skin infections and sepsis. The most common cause of death was found to be sepsis. CONCLUSIONS: AD-HIES and AR-HIES cannot be differentiated only based on the clinical presentations. Genetic features are also necessary for better diagnosis. This study, summarizing the clinical, immunological and genetic information of the patients with AD-HIES and AR-HIES, may open a way for better diagnosis and management of HIES.


Assuntos
Hipersensibilidade Alimentar/imunologia , Síndrome de Job/imunologia , Pneumonia/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Seguimentos , Hipersensibilidade Alimentar/genética , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Irã (Geográfico) , Síndrome de Job/genética , Masculino , Mutação/genética , Fenótipo , Pneumonia/genética , Fator de Transcrição STAT3/genética , Adulto Jovem
11.
Eur J Med Res ; 23(1): 61, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30587237

RESUMO

BACKGROUND: Recent studies have reported that endocrine-disrupting compound (EDC) exposure is related to food sensitization. Bisphenol A diglycidyl ether (BADGE) is one of the most widespread EDCs and its biological effects are considered to be greater on children than on adults. This study investigated the relationship between serum BADGE-specific immunoglobulin G (IgG) concentrations and food sensitization in young children by measuring food-specific IgE levels. METHODS: In total, 98 young children (59 boys and 39 girls; median age: 7 months; 25th and 75th percentile ages: 6 and 8 months, respectively) were enrolled. Blood samples were collected twice from all children (median sampling interval: 6 months; 25th and 75th percentile: 5 and 7 months). Food sensitization was evaluated based on food-specific IgE titers (egg white, milk, and wheat), which were determined using the capsulated hydrophilic carrier polymer-radioallergosorbent test. Furthermore, a dot-blotting assay for BADGE-specific IgG and quantitative reverse-transcriptase PCR for IL-6, IL-8, IL-10, and COX-2 mRNA expression were conducted. RESULTS: BADGE-specific IgG was detected in 20% of study subjects. A significant association was observed between the presence of BADGE-specific IgG and elevated wheat-specific IgE levels (OR = 3.56; 95% CI 1.13-11.2; P = 0.031). This relationship was particularly strong in girls (OR = 9.46; 95% CI 1.01-89.0; P = 0.049). A slight but non-significant association was noted between the presence of BADGE-specific IgG and elevated milk-specific IgE levels (OR = 2.77; 95% CI 0.93-8.22; P = 0.067). The expression of IL-6 mRNA among children with BADGE-specific IgG tended to increase, along with wheat-specific IgE levels. CONCLUSION: BADGE exposure might enhance food sensitization in early childhood. Therefore, this should be strictly regulated, especially in younger children.


Assuntos
Compostos Benzidrílicos/imunologia , Compostos de Epóxi/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Animais , Compostos Benzidrílicos/sangue , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Citocinas/genética , Citocinas/imunologia , Clara de Ovo , Compostos de Epóxi/sangue , Feminino , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/genética , Expressão Gênica/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Masculino , Leite/imunologia , Triticum/imunologia
12.
Front Immunol ; 9: 2414, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405614

RESUMO

Mast cells are highly versatile cells that perform a variety of functions depending on the immune trigger, context of activation, and cytokine stimulus. Antigen-mediated mast cell responses are regulated by transcriptional processes that result in the induction of numerous genes contributing to mast cell function. Recently, we also showed that exposure to dietary agents with known epigenetic actions such as curcumin can suppress mast cell-mediated food allergy, suggesting that mast cell responses in vivo may be epigenetically regulated. To further assess the effects of epigenetic modifications on mast cell function, we examined the behavior of bone marrow-derived mast cells (BMMCs) in response to trichostatin A (TSA) treatment, a well-studied histone deacetylase inhibitor. IgE-mediated BMMC activation resulted in enhanced expression and secretion of IL-4, IL-6, TNF-α, and IL-13. In contrast, pretreatment with TSA resulted in altered cytokine secretion. This was accompanied by decreased expression of FcεRI and mast cell degranulation. Interestingly, exposure to non-IgE stimuli such as IL-33, was also affected by TSA treatment. Furthermore, continuous TSA exposure contributed to mast cell apoptosis and a decrease in survival. Further examination revealed an increase in I-κBα and a decrease in phospho-relA levels in TSA-treated BMMCs, suggesting that TSA alters transcriptional processes, resulting in enhancement of I-κBα transcription and decreased NF-κB activation. Lastly, treatment of wild-type mice with TSA in a model of ovalbumin-induced food allergy resulted in a significant attenuation in the development of food allergy symptoms including decreases in allergic diarrhea and mast cell activation. These data therefore suggest that the epigenetic regulation of mast cell activation during immune responses may occur via altered histone acetylation, and that exposure to dietary substances may induce epigenetic modifications that modulate mast cell function.


Assuntos
Hipersensibilidade Alimentar/imunologia , Histonas/metabolismo , Mastócitos/imunologia , Acetilação , Animais , Apoptose , Células da Medula Óssea/citologia , Degranulação Celular , Sobrevivência Celular , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Epigênese Genética , Hipersensibilidade Alimentar/genética , Regulação da Expressão Gênica , Inibidores de Histona Desacetilases/metabolismo , Humanos , Ácidos Hidroxâmicos/metabolismo , Imunoglobulina E/metabolismo , Camundongos , NF-kappa B/metabolismo
13.
Clin Exp Immunol ; 194(1): 17-26, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30260469

RESUMO

Vitamin D receptor (VDR) mediates various biochemical activities between the cytoplasm and the nucleus in the cell. The nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) protein is involved in the T helper type 2 (Th2) response. This study tests a hypothesis that VDR interacts with NLRP3 to restrict the Th2-biased response. In this study, VDR-/- mice and WT (WT) mice were used. Th2 cell differentiation between VDR-/- mice and WT mice was observed. We observed that CD4+ T cell activation was higher in VDR-/- mice. The VDR-/-CD4+ T cells were prone to Th2 polarization. VDR-/- mice produced more immunoglobulin (Ig)E. VDR bound NLRP3 to prevent Th2 differentiation by restricting IL4 gene transcription. Th2 biased inflammation spontaneously developed in the intestine of VDR-/- mice. In conclusion, VDR binds NLRP3 to restrict IL4 gene transcription and prevent biased Th2 polarization.


Assuntos
Hipersensibilidade Alimentar/imunologia , Interleucina-4/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores de Calcitriol/metabolismo , Células Th2/imunologia , Adulto , Animais , Células Cultivadas , Feminino , Hipersensibilidade Alimentar/genética , Humanos , Interleucina-4/biossíntese , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ligação Proteica , Interferência de RNA , RNA Interferente Pequeno/genética , Receptores de Calcitriol/genética
14.
Immunol Lett ; 203: 87-94, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30194965

RESUMO

The skewed T helper (Th) 2 response plays a central role in the pathogenesis of allergic diseases, while its initiating factors remain elusive. Recent studies indicate that Bcl2 like protein-12 (Bcl2L12) is associated with the Th2-biased inflammation. This study is designed to test a hypothesis that Bcl2L12 plays a critical role in the initiation of allergic response. In this study, peripheral CD4+ T cells were isolated from food allergy (FA) patients and healthy subjects; A mouse FA model was developed to test the role of Bcl2L12 in induction of allergic response in the intestine. The results showed that expression of Bcl2L12 by CD4+ T cells was higher in FA patients and FA mice and positively correlated with expression of Th2 cytokines. CD4+ T cells from FA patients showed a Bcl2L12-dependent tendency to differentiate into Th2 cells. Bcl2L12 played a crucial role in induction of allergic response in the intestine. Physical contact between Bcl2L12 and GATA3 facilitated GATA3 to bind Il4 promoter to promote expression of IL-4. Adoptive transfer with Bcl2L12-deficient CD4+ T cells to Rag2¯/¯ mice did not reconstitute the efficient CD4+ T cell response as the mice could not be induced FA, while Rag2¯/¯ mice received WT CD4+ T cell transfer were induced FA. In conclusion, Bcl2L12 plays a crucial role in the induction of Th2 polarization and allergic response in the intestine. The Bcl2L12 in CD4+ T cells may be a potential target for the treatment of FA.


Assuntos
Hipersensibilidade Alimentar/imunologia , Mucosa Intestinal/imunologia , Proteínas Musculares/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Células Th2/imunologia , Adulto , Animais , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/patologia , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Humanos , Interleucina-4/genética , Interleucina-4/imunologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas Musculares/genética , Regiões Promotoras Genéticas/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Células Th2/patologia
15.
J Agric Food Chem ; 66(36): 9534-9541, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30139257

RESUMO

ß-Conglycinin (7S) and glycinin (11S) are known to induce a variety of hypersensitivity reactions involving the skin, intestinal tract, and respiratory tract. The present study aimed to identify the mechanism underlying the development of allergy to soybean antigen proteins, using piglets as an animal model. Weaned "Duroc × Landrace × Yorkshire" piglets were fed a diet supplemented with 7S or 11S to investigate the signaling pathway involved in intestinal damage in piglets. Results showed that serum nitric oxide (NO), tumor necrosis factor-α (TNF-α), and caspase-3 levels were significantly higher in 7S- and 11S-fed piglets compared to those in suckling or weaned ones. mRNA, protein, and phosphorylation levels of nuclear factor-kappa B (NF-κB), p38, and Jun N-terminal kinase (JNK) were higher in 7S- and 11S-fed piglets than in suckling and weaned ones. Overall, our results indicate that 7S and 11S damaged the intestinal function in piglets through their impact on NF-κB, JNK, and p38 expression.


Assuntos
Antígenos de Plantas/imunologia , Hipersensibilidade Alimentar/imunologia , Globulinas/imunologia , Intestinos/lesões , MAP Quinase Quinase 4/imunologia , NF-kappa B/imunologia , Proteínas de Armazenamento de Sementes/imunologia , Proteínas de Soja/imunologia , Soja/química , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Animais , Antígenos de Plantas/efeitos adversos , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/genética , Globulinas/efeitos adversos , Humanos , Intestinos/imunologia , MAP Quinase Quinase 4/genética , Sistema de Sinalização das MAP Quinases , NF-kappa B/genética , Proteínas de Armazenamento de Sementes/efeitos adversos , Proteínas de Soja/efeitos adversos , Soja/imunologia , Suínos , Proteínas Quinases p38 Ativadas por Mitógeno/genética
16.
Nat Commun ; 9(1): 3308, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120223

RESUMO

Food allergy poses a significant clinical and public health burden affecting 2-10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) underpins this suboptimal response. Infants who fail to resolve food allergy in later childhood exhibit cumulative increases in epigenetic disruption at T cell activation genes and poorer lymphoproliferative responses compared to children who resolved food allergy. Our data indicate epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex, and likely reflects pathways modified by gene-environment interactions in food allergy.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Epigênese Genética , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Ativação Linfocitária/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Análise por Conglomerados , Metilação de DNA/genética , Perfilação da Expressão Gênica , Humanos , Lactente , Polimorfismo Genético
18.
Rev Alerg Mex ; 65(2): 187-191, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-29983016

RESUMO

BACKGROUND: Food additives are intentionally-added ingredients in order to modify physical, chemical, biological, or sensory characteristics of foods. Allergic reactions caused by additives are uncommon in children, and their prevalence is not known; however, they can be severe. CASE REPORT: An 8-year-old male presented with anaphylaxis and recurrent anaphylactic shocks due to multiple triggering factors such as food additives and medications. Point-of-care skin tests were performed with several additives, with positive results. Personalized emergency treatment was indicated in view of the possibility of anaphylaxis (adrenaline, diphenhydramine and dexamethasone) and environmental care for aeroallergens. Owing to a history of adverse reaction to salbutamol (giant or generalized urticaria), formoterol dry powder was indicated, which was well tolerated. Organic food exclusive consumption was recommended. CONCLUSIONS: The diagnosis of allergy to additives should be suspected when the patient has a suggestive medical history, allergy to multiple foods or medications, reaction with manufactured foods, unrelated to organic products.


Assuntos
Aditivos Alimentares/efeitos adversos , Hipersensibilidade Alimentar/etiologia , Criança , Hipersensibilidade Alimentar/genética , Humanos , Hipersensibilidade/genética , Masculino , Linhagem
19.
Clin Exp Allergy ; 48(10): 1345-1353, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29974988

RESUMO

BACKGROUND: Failure to induce oral tolerance may result in food allergy. Hydrolysed cow's milk-based infant formulas are recommended in subjects with a high risk of developing allergic disease. Presentation of T cell epitopes is a prerequisite to generate regulatory T cells that could contribute to oral tolerance. OBJECTIVE: To investigate whether a specific hydrolysed whey-based infant formula contains peptides that function as T cell epitopes to support the development of oral tolerance to whey. METHODS: First, a novel liquid chromatography-mass spectrometry (LC-MS) method was developed to characterize ß-lactoglobulin-derived peptides present in a specific infant formula with a focus on region AA#13-48 of ß-lactoglobulin, which has previously been described to contain T cell epitopes with tolerogenic potential. Second, the formula was subjected to the ProImmune ProPresent® antigen presentation assay and MHC class II binding algorithm to identify relevant HLA-DRB1-restricted peptides. Third, identified peptides were tested on human cow's milk protein-specific T cell lines to determine T cell recognition. RESULTS: Thirteen peptides of minimal 9AAs long that overlap with AA#13-48 of ß-lactoglobulin were identified. Six of them were found across all batches analysed. It was further confirmed that these peptides were processed and presented by human dendritic cells. The identified HLA-DRB1-restricted peptides were correlated to AA#11-30 and AA#23-39 of ß-lactoglobulin. Importantly, the proliferation assay showed that the synthetic peptides were recognized by cow's milk protein-specific T cell lines and induced T cell proliferation. CONCLUSION AND CLINICAL RELEVANCE: This study demonstrates that the tested hydrolysed infant formula contains functional HLA-DRB1-restricted T cell epitopes, which can potentially support the development of oral tolerance to whey.


Assuntos
Tolerância Imunológica , Fórmulas Infantis , Peptídeos/imunologia , Proteínas do Soro do Leite , Sequência de Aminoácidos , Animais , Apresentação do Antígeno/imunologia , Bovinos , Cromatografia Líquida , Mapeamento de Epitopos , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/prevenção & controle , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Hidrólise , Lactente , Fórmulas Infantis/efeitos adversos , Ativação Linfocitária/imunologia , Espectrometria de Massas , Leite/imunologia , Proteínas do Leite/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Proteínas do Soro do Leite/química , Proteínas do Soro do Leite/imunologia
20.
J Agric Food Chem ; 66(22): 5581-5592, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29763312

RESUMO

Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.


Assuntos
4-Butirolactona/análogos & derivados , Anafilaxia/tratamento farmacológico , Aspergillus/química , Hipersensibilidade Alimentar/tratamento farmacológico , Mastócitos/imunologia , 4-Butirolactona/administração & dosagem , Anafilaxia/genética , Anafilaxia/imunologia , Animais , Aspergillus/genética , Aspergillus/isolamento & purificação , Células Cultivadas , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Histamina/imunologia , Humanos , Imunoglobulina E/imunologia , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Água do Mar/microbiologia
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