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1.
Handb Exp Pharmacol ; 268: 331-357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34223997

RESUMO

There has been a substantial increase in the incidence and the prevalence of allergic disorders in the recent decades, which seems to be related to rapid environmental and lifestyle changes, such as higher exposure to factors thought to exert pro-allergic effects but less contact with factors known to be associated with protection against the development of allergies. Pollution is the most remarkable example of the former, while less contact with microorganisms, lower proportion of unprocessed natural products in diet, and others resulting from urbanization and westernization of the lifestyle exemplify the latter. It is strongly believed that the effects of environmental factors on allergy susceptibility and development are mediated by epigenetic mechanisms, i.e. biologically relevant biochemical changes of the chromatin carrying transcriptionally-relevant information but not affecting the nucleotide sequence of the genome. Classical epigenetic mechanisms include DNA methylation and histone modifications, for instance acetylation or methylation. In addition, microRNA controls gene expression at the mRNA level. Such epigenetic mechanisms are involved in crucial regulatory processes in cells playing a pivotal role in allergies. Those include centrally managing cells, such as T lymphocytes, as well as specific structural and effector cells in the affected organs, responsible for the local clinical presentation of allergy, e.g. epithelial or airway smooth muscle cells in asthma. Considering that allergic disorders possess multiple clinical (phenotypes) and mechanistic (endotypes) forms, targeted, stratified treatment strategies based on detailed clinical and molecular diagnostics are required. Since conventional diagnostic or therapeutic approaches do not suffice, this gap could possibly be filled out by epigenetic approaches.


Assuntos
Asma , Hipersensibilidade , Metilação de DNA , Epigênese Genética , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/genética , Hipersensibilidade/prevenção & controle , Processamento de Proteína Pós-Traducional
2.
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
4.
Artigo em Inglês | MEDLINE | ID: mdl-34455626

RESUMO

BACKGROUND: While childhood asthma prevalence is rising in Westernized countries, farm children are protected. The mitogen-activated protein kinase (MAPK) pathway with its negative regulator dual-specificity phosphatase-1 (DUSP1) is presumably associated with asthma development. OBJECTIVES: We aimed to investigate the role of MAPK signaling in childhood asthma and its environment-mediated protection, including a representative selection of 232 out of 1062 children from two cross-sectional cohorts and one birth cohort study. METHODS: Peripheral blood mononuclear cells (PBMC) from asthmatic and healthy children were cultured upon stimulation with farm-dust extracts or lipopolysaccharide. In subgroups, gene expression was analyzed by qPCR (PBMCs, cord blood) and NanoString technology (dendritic cells). Protein expression of phosphorylated MAPKs was measured by mass cytometry. Histone acetylation was investigated by chromatin immunoprecipitation. RESULTS: Asthmatic children expressed significantly less DUSP1 (p = .006) with reduced acetylation at histone H4 (p = .012) compared with healthy controls. Farm-dust stimulation upregulated DUSP1 expression reaching healthy levels and downregulated inflammatory MAPKs on gene and protein levels (PBMCs; p ≤ .01). Single-cell protein analysis revealed downregulated pMAPKs upon farm-dust stimulation in B cells, NK cells, monocytes, and T-cell subpopulations. CONCLUSION: Lower DUSP1 baseline levels in asthmatic children and anti-inflammatory regulation of MAPK in several immune cell types by farm-dust stimulation indicate a regulatory function for DUSP1 for future therapy contributing to anti-inflammatory characteristics of farming environments.

5.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067156

RESUMO

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.


Assuntos
Asma/metabolismo , Vesículas Extracelulares/metabolismo , Animais , Asma/genética , Asma/microbiologia , Asma/fisiopatologia , Biomarcadores/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos
6.
Front Immunol ; 12: 637087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815389

RESUMO

During its 30 years history, the Hygiene Hypothesis has shown itself to be adaptable whenever it has been challenged by new scientific developments and this is a still a continuously ongoing process. In this regard, the mini review aims to discuss some selected new developments in relation to their impact on further fine-tuning and expansion of the Hygiene Hypothesis. This will include the role of recently discovered classes of innate and adaptive immune cells that challenges the old Th1/Th2 paradigm, the applicability of the Hygiene Hypothesis to newly identified allergy/asthma phenotypes with diverse underlying pathomechanistic endotypes, and the increasing knowledge derived from epigenetic studies that leads to better understanding of mechanisms involved in the translation of environmental impacts on biological systems. Further, we discuss in brief the expansion of the Hygiene Hypothesis to other disease areas like psychiatric disorders and cancer and conclude that the continuously developing Hygiene Hypothesis may provide a more generalized explanation for health burden in highly industrialized countries also relation to global changes.


Assuntos
Asma/imunologia , Hipótese da Higiene , Hipersensibilidade/imunologia , Transtornos Mentais/imunologia , Animais , Países Desenvolvidos , Exposição Ambiental , Carga Global da Doença , Humanos , Equilíbrio Th1-Th2
7.
Front Immunol ; 12: 635935, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796103

RESUMO

Postulated by Strachan more than 30 years ago, the Hygiene Hypothesis has undergone many revisions and adaptations. This review journeys back to the beginnings of the Hygiene Hypothesis and describes the most important landmarks in its development considering the many aspects that have refined and generalized the Hygiene Hypothesis over time. From an epidemiological perspective, the Hygiene Hypothesis advanced to a comprehensive concept expanding beyond the initial focus on allergies. The Hygiene Hypothesis comprise immunological, microbiological and evolutionary aspects. Thus, the original postulate developed into a holistic model that explains the impact of post-modern life-style on humans, who initially evolved in close proximity to a more natural environment. Focusing on diet and the microbiome as the most prominent exogenous influences we describe these discrepancies and the resulting health outcomes and point to potential solutions to reestablish the immunological homeostasis that frequently have been lost in people living in developed societies.


Assuntos
Imunidade Adaptativa , Bactérias/imunologia , Microbioma Gastrointestinal/imunologia , Hipótese da Higiene , Imunidade Inata , Linfócitos T/imunologia , Animais , Asma/imunologia , Asma/microbiologia , Bactérias/patogenicidade , Dieta/efeitos adversos , Disbiose , Evolução Molecular , História do Século XX , História do Século XXI , Interações Hospedeiro-Patógeno , Humanos , Hipótese da Higiene/história , Tolerância Imunológica , Fenótipo , Linfócitos T/metabolismo , Linfócitos T/microbiologia
8.
Cell Rep ; 35(1): 108956, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33826881

RESUMO

Extensive remodeling of the airways is a major characteristic of chronic inflammatory lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). To elucidate the importance of a deregulated immune response in the airways for remodeling processes, we established a matching Drosophila model. Here, triggering the Imd (immune deficiency) pathway in tracheal cells induced organ-wide remodeling. This structural remodeling comprises disorganization of epithelial structures and comprehensive epithelial thickening. We show that these structural changes do not depend on the Imd pathway's canonical branch terminating on nuclear factor κB (NF-κB) activation. Instead, activation of a different segment of the Imd pathway that branches off downstream of Tak1 and comprises activation of c-Jun N-terminal kinase (JNK) and forkhead transcription factor of the O subgroup (FoxO) signaling is necessary and sufficient to mediate the observed structural changes of the airways. Our findings imply that targeting JNK and FoxO signaling in the airways could be a promising strategy to interfere with disease-associated airway remodeling processes.

9.
J Allergy Clin Immunol ; 148(3): 843-857.e6, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33684437

RESUMO

BACKGROUND: Prenatal exposure to infections can modify immune development. These environmental disturbances during early life potentially alter the incidence of inflammatory disorders as well as priming of immune responses. Infection with the helminth Schistosoma mansoni is widely studied for its ability to alter immune responsiveness and is associated with variations in coinfection, allergy, and vaccine efficacy in endemic populations. OBJECTIVE: Exposure to maternal schistosomiasis during early life, even without transmission of infection, can result in priming effects on offspring immune responses to bystander antigenic challenges as related to allergic responsiveness and vaccination, with this article seeking to further clarify the effects and underlying immunologic imprinting. METHODS: Here, we have combined a model of chronic maternal schistosomiasis infection with a thorough analysis of subsequent offspring immune responses to allergy and vaccination models, including viral challenge and steady-state changes to immune cell compartments. RESULTS: We have demonstrated that maternal schistosomiasis alters CD4+ responses during allergic sensitization and challenge in a skewed IL-4/B-cell-dominant response to antigenic challenge associated with limited inflammatory response. Beyond that, we have uncovered previously unidentified alterations to CD8+ T-cell responses during immunization that are dependent on vaccine formulation and have functional impact on the efficacy of vaccination against viral infection in a murine hepatitis B virus model. CONCLUSION: In addition to steady-state modifications to CD4+ T-cell polarization and B-cell priming, we have traced these modified CD8+ responses to an altered dendritic cell phenotype sustained into adulthood, providing evidence for complex priming effects imparted by infection via fetomaternal cross talk.


Assuntos
Efeitos Tardios da Exposição Pré-Natal/imunologia , Hipersensibilidade Respiratória/imunologia , Esquistossomose/imunologia , Alérgenos/imunologia , Animais , Linfócitos B/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Feminino , Feto/imunologia , Perfilação da Expressão Gênica , Imunização , Pulmão/imunologia , Linfonodos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Gravidez , Hipersensibilidade Respiratória/genética , Schistosoma mansoni , Baço/imunologia , Linfócitos T/imunologia
10.
Nutrients ; 13(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668787

RESUMO

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.


Assuntos
Epigênese Genética/imunologia , Hipersensibilidade , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Materna , Feminino , Humanos , Recém-Nascido , Gravidez
11.
Allergy ; 76(8): 2461-2474, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33528894

RESUMO

BACKGROUND: While several systemic immunomodulatory effects of allergen-specific immunotherapy (AIT) have been discovered, local anti-inflammatory mechanisms in the respiratory tract are largely unknown. We sought to elucidate local and epithelial mechanisms underlying allergen-specific immunotherapy in a genome-wide approach. METHODS: We induced sputum in hay fever patients and healthy controls during the pollen peak season and stratified patients by effective allergen immunotherapy or as untreated. Sputum was directly processed after induction and subjected to whole transcriptome RNA microarray analysis. Nasal secretions were analyzed for Secretoglobin1A1 (SCGB1A1) and IL-24 protein levels in an additional validation cohort at three defined time points during the 3-year course of AIT. Subsequently, RNA was extracted and subjected to an array-based whole transcriptome analysis. RESULTS: Allergen-specific immunotherapy inhibited pro-inflammatory CXCL8, IL24, and CCL26mRNA expression, while SCGB1A1, IL7, CCL5, CCL23, and WNT5BmRNAs were induced independently of the asthma status and allergen season. In our validation cohort, local increase of SCGB1A1 occurred concomitantly with the reduction of local IL-24 in upper airways during the course of AIT. Additionally, SCGB1A1 was identified as a suppressor of epithelial gene expression. CONCLUSIONS: Allergen-specific immunotherapy induces a yet unknown local gene expression footprint in the lower airways that on one hand appears to be a result of multiple regulatory pathways and on the other hand reveals SCGB1A1 as novel anti-inflammatory mediator of long-term allergen-specific therapeutic intervention in the local environment.


Assuntos
Dessensibilização Imunológica , Rinite Alérgica Sazonal , Uteroglobina/metabolismo , Alérgenos , Humanos , Sistema Respiratório
12.
Allergy ; 76(4): 1010-1023, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33128851

RESUMO

Allergic diseases of the (upper and lower) airways, the skin and the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity, and increased healthcare costs. As allergic diseases are mostly tissue-specific, local sampling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local sampling using noninvasive or minimally invasive methods can be cost-effective and well tolerated, which may even be suitable for primary or home care sampling. Non- or minimally invasive local sampling and diagnostics may enable a more thorough endotyping, may help to avoid under- or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood samples may help to facilitate minimal-invasive primary or home care sampling for classical systemic diagnostic approaches. This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which samples or matrices can be used. Based on this assessment, EAACI position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments.


Assuntos
Hipersensibilidade , Qualidade de Vida , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Sistema Respiratório , Pele
13.
Front Immunol ; 11: 561724, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224135

RESUMO

Endogenous redox systems not only counteract oxidative damage induced by high levels of hydroxyl radicals (OH·) under pathological conditions, but also shape redox signaling as a key player in the regulation of physiological processes. Second messengers like hydrogen peroxide and nitric oxide, as well as redox enzymes of the Thioredoxin (Trx) family, including Trxs, glutaredoxins (Grxs), and peroxiredoxins (Prxs) modulate reversible, oxidative modifications of proteins. Thereby redox regulation is part of various cellular processes such as the immune response and Trx proteins have been linked in different disorders including inflammatory diseases. Here, we have analyzed the protein distribution of representative oxidoreductases of the Trx fold protein family-Trx1, Grx1, Grx2, and Prx2-in a murine model of allergic asthma bronchiale, as well as their potential therapeutic impact on type-2 driven airway inflammation. Ovalbumin (OVA) sensitization and challenge using the type-2 prone Balb/c mouse strain resulted in increased levels of all investigated proteins in distinct cellular patterns. While concomitant treatment with Grx1 and Prx2 did not show any therapeutic impact on the outcome of the disease, Grx2 or Trx1 treatment before and during the OVA challenge phase displayed pronounced protective effects on the manifestation of allergic airway inflammation. Eosinophil numbers and the type-2 cytokine IL-5 were significantly reduced while lung function parameters profoundly improved. The number of macrophages in the bronchoalveolar lavage (BAL) did not change significantly, however, the release of nitric oxide that was linked to airway inflammation was successfully prevented by enzymatically active Grx2 ex vivo. The Grx2 Cys-X-X-Ser mutant that facilitates de-/glutathionylation, but does not catalyze dithiol/disulfide exchange lost the ability to protect from airway hyper reactivity and to decrease NO release by macrophages, however, it reduced the number of infiltrating immune cells and IL-5 release. Altogether, this study demonstrates that specific redox proteins and particular enzyme activities protect against inflammatory damage. During OVA-induced allergic airway inflammation, administration of Grx2 exerts beneficial and thus potentially therapeutic effects.


Assuntos
Asma/sangue , Asma/tratamento farmacológico , Glutarredoxinas/administração & dosagem , Glutarredoxinas/sangue , Substâncias Protetoras/administração & dosagem , Animais , Asma/induzido quimicamente , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Ovalbumina/farmacologia , Oxirredução/efeitos dos fármacos , Células RAW 264.7 , Proteínas Recombinantes/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Tiorredoxinas/administração & dosagem
14.
Nutrients ; 12(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086571

RESUMO

Immunoglobulin E (IgE)-mediated allergy against cow's milk protein fractions such as whey is one of the most common food-related allergic disorders of early childhood. Histone acetylation is an important epigenetic mechanism, shown to be involved in the pathogenesis of allergies. However, its role in food allergy remains unknown. IgE-mediated cow's milk allergy was successfully induced in a mouse model, as demonstrated by acute allergic symptoms, whey-specific IgE in serum, and the activation of mast cells upon a challenge with whey protein. The elicited allergic response coincided with reduced percentages of regulatory T (Treg) and T helper 17 (Th17) cells, matching decreased levels of H3 and/or H4 histone acetylation at pivotal Treg and Th17 loci, an epigenetic status favoring lower gene expression. In addition, histone acetylation levels at the crucial T helper 1 (Th1) loci were decreased, most probably preceding the expected reduction in Th1 cells after inducing an allergic response. No changes were observed for T helper 2 cells. However, increased histone acetylation levels, promoting gene expression, were observed at the signal transducer and activator of transcription 6 (Stat6) gene, a proallergic B cell locus, which was in line with the presence of whey-specific IgE. In conclusion, the observed histone acetylation changes are pathobiologically in line with the successful induction of cow's milk allergy, to which they might have also contributed mechanistically.


Assuntos
Histonas/metabolismo , Imunoglobulina E/imunologia , Hipersensibilidade a Leite/imunologia , Células Th1 , Acetilação , Animais , Linfócitos B/imunologia , Modelos Animais de Doenças , Epigenômica , Feminino , Expressão Gênica , Imunoglobulina E/sangue , Mastócitos/imunologia , Camundongos Endogâmicos C3H , Hipersensibilidade a Leite/genética , Fator de Transcrição STAT6 , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Soro do Leite/imunologia
15.
Front Immunol ; 11: 1747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973742

RESUMO

Asthma is a chronic inflammatory disease of the respiratory tract characterized by recurrent breathing problems resulting from airway obstruction and hyperresponsiveness. Human airway epithelium plays an important role in the initiation and control of the immune responses to different types of environmental factors contributing to asthma pathogenesis. Using pattern recognition receptors airway epithelium senses external stimuli, such as allergens, microbes, or pollutants, and subsequently secretes endogenous danger signaling molecules alarming and activating dendritic cells. Hence, airway epithelial cells not only mediate innate immune responses but also bridge them with adaptive immune responses involving T and B cells that play a crucial role in the pathogenesis of asthma. The effects of environmental factors on the development of asthma are mediated, at least in part, by epigenetic mechanisms. Those comprise classical epigenetics including DNA methylation and histone modifications affecting transcription, as well as microRNAs influencing translation. The common feature of such mechanisms is that they regulate gene expression without affecting the nucleotide sequence of the genomic DNA. Epigenetic mechanisms play a pivotal role in the regulation of different cell populations involved in asthma pathogenesis, with the remarkable example of T cells. Recently, however, there is increasing evidence that epigenetic mechanisms are also crucial for the regulation of airway epithelial cells, especially in the context of epigenetic transfer of environmental effects contributing to asthma pathogenesis. In this review, we summarize the accumulating evidence for this very important aspect of airway epithelial cell pathobiology.


Assuntos
Asma/genética , Asma/imunologia , Epigênese Genética , Células Epiteliais/imunologia , Pulmão/imunologia , Acetilação , Animais , Asma/metabolismo , Asma/fisiopatologia , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Broncoconstrição , Metilação de DNA , Células Epiteliais/metabolismo , Histonas/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/fisiopatologia , MicroRNAs/genética , MicroRNAs/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais
17.
Cell Signal ; 69: 109523, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31904412

RESUMO

The term (bronchial) asthma describes a disorder syndrome that comprises several disease phenotypes, all characterized by chronic inflammation in the bronchial epithelium, with a variety of subsequent functional consequences. Thus, the epithelium in the conducting airways is the main localization of the complex pathological changes in the disease. In this regard, bronchial epithelial cells are not passively affected by inflammatory mechanisms induced by immunological processes but rather actively involved in all steps of disease development from initiation and perpetuation to chronification. In recent years it turned out that bronchial epithelial cells show a high level of structural and functional diversity and plasticity with epigenetic mechanisms playing a crucial role in the regulation of these processes. Thus, it is quite reasonable that differential functional activities of the bronchial epithelium are involved in the development of different asthma phenotypes and/or stages of disease. The current knowledge on this topic will be discussed in this review article.


Assuntos
Asma , Brônquios , Células Epiteliais , Inflamação , Animais , Asma/metabolismo , Asma/patologia , Brônquios/metabolismo , Brônquios/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Epitélio/metabolismo , Epitélio/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia
18.
Allergy ; 75(3): 497-523, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31520486

RESUMO

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes.


Assuntos
Asma , Hipersensibilidade , Asma/epidemiologia , Asma/etiologia , Asma/prevenção & controle , Criança , Dieta , Feminino , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/prevenção & controle , Lactente , Gravidez
19.
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
20.
Allergy ; 74(8): 1429-1444, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31032983

RESUMO

The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid-associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis.


Assuntos
Asma/metabolismo , Dermatite Atópica/metabolismo , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Hipersensibilidade Alimentar/metabolismo , Adulto , Fatores Etários , Animais , Asma/epidemiologia , Asma/etiologia , Asma/prevenção & controle , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Dermatite Atópica/prevenção & controle , Modelos Animais de Doenças , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/prevenção & controle , Humanos , Imunomodulação , Lactente , Recém-Nascido , Metabolismo dos Lipídeos , Transdução de Sinais
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