Identification of extracellular vesicle microRNA signatures specifically linked to inflammatory and metabolic mechanisms in obesity-associated low type-2 asthma.

Rationale And Objective: Plasma extracellular vesicles (EVs) represent a vital source of molecular information about health and disease states. Due to their heterogenous cellular sources, EVs and their cargo may predict specific pathomechanisms behind disease phenotypes. Here we aimed to utilize EV microRNA (miRNA) signatures to gain new insights into underlying molecular mechanisms of obesity-associated low type-2 asthma.

IL-17A-producing CD8 T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8 T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC.

Immune Responsiveness to LPS Determines Risk of Childhood Wheeze and Asthma in 17q21 Risk Allele Carriers.

In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in  = 445 children.

Differential Regulation of Interferon Signaling Pathways in CD4 T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype.

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.

The Hygiene Hypothesis and New Perspectives-Current Challenges Meeting an Old Postulate.

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.

Author Correction: Farm-like indoor microbiota in non-farm homes protects children from asthma development.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Farm-like indoor microbiota in non-farm homes protects children from asthma development.

Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today. The asthma-protective effect of farms appears to be associated with rich home dust microbiota, which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases.

Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes.

Adipocytes express various pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and actively participate in anti-bacterial and anti-viral host defence. Obesity is associated with adipose tissue PRR expression. The potential role of Toll-like receptor 9 (TLR9) in adipocytes has not yet been investigated.

Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood.

Importance: Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking.

Objective: To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases.

ω-3 fatty acids contribute to the asthma-protective effect of unprocessed cow's milk.

Background: Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown.

Epigenetic Regulation in Early Childhood: A Miniaturized and Validated Method to Assess Histone Acetylation.

Introduction: Chronic inflammatory diseases including allergies and asthma are the result of complex interactions between genes and environmental factors. Epigenetic mechanisms comprise a set of biochemical reactions that regulate gene expression. In order to understand the cause-effect relationship between environmental exposures and disease development, methods capable of assessing epigenetic regulation (also) in large cohorts are needed.

The Early Development of Wheeze. Environmental Determinants and Genetic Susceptibility at 17q21.

Rationale: Growing up on a farm protects from childhood asthma and early wheeze. Virus-triggered wheeze in infancy predicts asthma in individuals with a genetic asthma risk associated with chromosome 17q21.

Objectives: To test environmental determinants of infections and wheeze in the first year of life, potential modifications of these associations by 17q21, and the implications for different trajectories of wheeze.

Consumption of unprocessed cow's milk protects infants from common respiratory infections.

Background: Breast-feeding is protective against respiratory infections in early life. Given the co-evolutionary adaptations of humans and cattle, bovine milk might exert similar anti-infective effects in human infants.

Objective: To study effects of consumption of raw and processed cow's milk on common infections in infants.

Bioavailability and allergoprotective capacity of milk-associated conjugated linoleic acid in a murine model of allergic airway inflammation.

Background: Cross-sectional epidemiological studies have demonstrated that farm milk from traditional farm settings possesses allergoprotective properties. Up to now, it has not been clarified which milk ingredient is responsible for protection against allergic diseases. As farm milk is rich in conjugated linoleic acids (CLA), it is hypothesized that this n-3 polyunsaturated fatty acid family contributes to the allergoprotective capacity of farm milk.

The mucosal microbiome in shaping health and disease.

More than 300 years after Antonie van Leeuwenhoek gave the first description of microbes that colonize human body surfaces, the re-discovery of this multifaceted microbial world within our bodies has challenged our principal view on microbes. Novel sequencing techniques provide a plethora of (meta)genomic data, which elucidate the unique properties of mircobiota in different subjects. Moreover, the variety of metabolic and immunologic interactions between the mircobiota and the host's epithelial surfaces has challenged the paradigm of a unidirectional interplay between a given pathogen and the host's immune defense.

Microbial exposure and onset of allergic diseases - potential prevention strategies?

Chronic inflammatory diseases are a major health problem with global dimension. Particularly, the incidence of allergic diseases has been increased tremendously within the last decades. This world-wide trend clearly indicates the demand for new approaches in the investigation of early allergy development.

Clinical and epidemiologic phenotypes of childhood asthma.

Rationale: Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes.

Objectives: To compare epidemiologic phenotype definitions identified by latent class analysis (LCA) with clinical phenotypes based on patient histories, diagnostic work-up, and treatment responses. To relate phenotypes to genetic and environmental determinants as well as diagnostic and treatment-related parameters.

Microbial influence on tolerance and opportunities for intervention with prebiotics/probiotics and bacterial lysates.

Epidemiologic studies indicate that microbes and microbial components are associated with protection against chronic inflammatory disease. Consequently, a plethora of clinical approaches have been used to investigate the benefits of a range of microbial products on inflammatory conditions in human trials. Centered particularly on the use of prebiotics, probiotic bacteria, and bacterial lysates in early life, this review provides an overview on clinical approaches aimed at reducing the global burden of allergic disease through primary prevention.

Inflammatory response and IgE sensitization at early age.

Background: Microbial exposure may induce low-grade inflammation at an early age and decrease the risk of allergic diseases, as suggested by the hygiene hypothesis. We examined the associations between low-grade inflammation and the development of allergic sensitization, atopic dermatitis (AD), and asthma at the age of 4.5 yr.

High indoor microbial levels are associated with reduced Th1 cytokine secretion capacity in infancy.

Background: Exposure to microbes and their components may affect the maturation of the immune system. We examined the association of house dust microbial content with cytokine-producing capacity at birth and at the age of 1 year.

Methods: Production of TNF-α, IFN-γ, IL-5, IL-8 and IL-10 at birth (n = 228) and at the age of 1 year (n = 200) following 24- and 48-hour whole-blood stimulation with staphylococcal enterotoxin B (SEB), lipopolysaccharide and the combination of phorbol ester and ionomycin was measured.