Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue.

Metabolic disorders, such as obesity and type 2 diabetes have a large impact on global health, especially in industrialized countries. Tissue-specific chronic low-grade inflammation is a key contributor to complications in metabolic disorders. To support therapeutic approaches to these complications, it is crucial to gain a deeper understanding of the inflammatory dynamics and to monitor them on the individual level.

Nanomaterials and the Serosal Immune System in the Thoracic and Peritoneal Cavities.

The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria.

Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation.

A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into prophylactic or therapeutic approaches, there is no regulatory guidance on how to assess the risk and benefit balance of such interventions.

Network-Based Selection of Candidate Markers and Assays to Assess the Impact of Oral Immune Interventions on Gut Functions.

To assess the safety and efficacy of oral immune interventions, it is important and required by regulation to assess the impact of those interventions not only on the immune system, but also on other organs such as the gut as the porte d'entrée. Despite clear indications that the immune system interacts with several physiological functions of the gut, it is still unknown which pathways and molecules are crucial to assessing the impact of nutritional immune interventions on gut functioning. Here we used a network-based systems biology approach to clarify the molecular relationships between immune system and gut functioning and to identify crucial biomarkers to assess effects on gut functions upon nutritional immune interventions.

Current and Future Nutritional Strategies to Modulate Inflammatory Dynamics in Metabolic Disorders.

Obesity, type 2 diabetes, and other metabolic disorders have a large impact on global health, especially in Western countries. An important hallmark of metabolic disorders is chronic low-grade inflammation. A key player in chronic low-grade inflammation is dysmetabolism, which is defined as the inability to keep homeostasis resulting in loss of lipid control, oxidative stress, inflammation, and insulin resistance.

Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?

Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection.

A network-based approach for identifying suitable biomarkers for oral immunotherapy of food allergy.

Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, concerns with regards to safety and long-term efficacy of OIT remain. There is a need to identify biomarkers that predict, monitor and/or evaluate the effects of OIT.

The Impact of Immune Interventions: A Systems Biology Strategy for Predicting Adverse and Beneficial Immune Effects.

Despite scientific advances it remains difficult to predict the risk and benefit balance of immune interventions. Since a few years, network models have been built based on comprehensive datasets at multiple molecular/cellular levels (genes, gene products, metabolic intermediates, macromolecules, cells) to illuminate functional and structural relationships. Here we used a systems biology approach to identify key immune pathways involved in immune health endpoints and rank crucial candidate biomarkers to predict adverse and beneficial effects of nutritional immune interventions.

The Serosal Immune System of the Thorax in Toxicology.

The thoracic cavities receive increasing attention in toxicology, because inhaled fibers and (nano)particles can reach these cavities and challenge the local lymphoid tissues. The thoracic and abdominopelvic cavities are controlled by the serosal immune system with its special, loosely organized lymphoid clusters, namely the fat-associated lymphoid clusters and milky spots, which together can be denoted as serosa-associated lymphoid clusters. These clusters house numerous innate lymphoid cells, namely the nonconventional, innate B lymphoid cell and innate lymphocyte type 2 populations.

Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins.

Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization.

Evaluation of the sensitizing potential of food proteins using two mouse models.

The current methodology to identify allergenic food proteins is effective in identifying those that are likely to cross-react with known allergens. However, most assays show false positive results for low/non-allergens. Therefore, an ex vivo/in vitro DC-T cell assay and an in vivo mouse model were used to distinguish known allergenic food proteins (Ara h 1, β-Lactoglobulin, Pan b 1, bovine serum albumin, whey protein isolate) from low/non allergenic food proteins (soy lipoxygenase, gelatin, beef tropomyosin, rubisco, Sola t 1).

Modifying the infant's diet to prevent food allergy.

Recommendations and guidelines on the prevention of food allergy have changed in recent decades. The aim of this review of the current evidence and ongoing studies is to provide a comprehensive and up to date picture of prevention of food allergy for healthcare professionals. The review was undertaken as part of the European Union funded Integrated Approaches to Food Allergy and Allergen Management (iFAAM) study.

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models.

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins.

Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.

A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human.

The protein structure determines the sensitizing capacity of Brazil nut 2S albumin (Ber e1) in a rat food allergy model.

: It is not exactly known why certain food proteins are more likely to sensitize. One of the characteristics of most food allergens is that they are stable to the acidic and proteolytic conditions in the digestive tract. This property is thought to be a risk factor in allergic sensitization.

Digestibility of transglutaminase cross-linked caseinate versus native caseinate in an in vitro multicompartmental model simulating young child and adult gastrointestinal conditions.

Aim of this study was to investigate the digestion of transglutaminase cross-linked caseinate (XLC) versus native caseinate (NC) in solution and in cheese spread under digestive conditions for adults and children mimicked in a gastrointestinal model. Samples were collected for gel electrophoresis and nitrogen analysis. The results showed no relevant differences between XLC and NC for total and α-amino nitrogen in digested fraction under adult and child conditions.

Immunomodulatory effects of potential probiotics in a mouse peanut sensitization model.

Peanut allergy accounts for the majority of severe food-related allergic reactions and there is a need for new prevention and treatment strategies. Probiotics may be considered for treatment on the basis of their immunomodulating properties. Cytokine profiles of probiotic strains were determined by in vitro co-culture with human PBMCs.

Integration of efficacy, pharmacokinetic and safety assessment of interleukin-1 receptor antagonist in a preclinical model of arthritis.

Pharmacokinetic properties and safety profile of a drug are likely influenced by the disease state of a patient. In this study, we investigated the influence of arthritic processes on pharmacokinetics and immunotoxicity of interleukin-1 receptor antagonist (Anakinra) in the rat adjuvant arthritis model. Anakinra dose-dependently suppressed joint inflammation and degradation as demonstrated by reduced clinical arthritis score, paw thickness, synovial infiltration and bone degradation.

Identification of genetic loci in Lactobacillus plantarum that modulate the immune response of dendritic cells using comparative genome hybridization.

Background: Probiotics can be used to stimulate or regulate epithelial and immune cells of the intestinal mucosa and generate beneficial mucosal immunomodulatory effects. Beneficial effects of specific strains of probiotics have been established in the treatment and prevention of various intestinal disorders, including allergic diseases and diarrhea. However, the precise molecular mechanisms and the strain-dependent factors involved are poorly understood.

Novel self-epitopes derived from aggrecan, fibrillin, and matrix metalloproteinase-3 drive distinct autoreactive T-cell responses in juvenile idiopathic arthritis and in health.

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by chronic joint inflammation. Knowing which antigens drive the autoreactive T-cell response in JIA is crucial for the understanding of disease pathogenesis and additionally may provide targets for antigen-specific immune therapy. In this study, we tested 9 self-peptides derived from joint-related autoantigens for T-cell recognition (T-cell proliferative responses and cytokine production) in 36 JIA patients and 15 healthy controls.

Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans.

Expression of the transcription factor Foxp3 (forkhead box P3) has been implicated as a key element for CD25(+) T regulatory cell function in mice. However, literature over similar involvement of FOXP3 expression in human T regulatory cells is limited. We found that, unlike murine cells, FOXP3 mRNA expression could be induced in human CD25(-) and CD8(+) peripheral blood mononuclear cells, which were both negative for FOXP3 mRNA expression after isolation.

Functional regulatory immune responses against human cartilage glycoprotein-39 in health vs. proinflammatory responses in rheumatoid arthritis.

The class of immune response against autoantigens could profoundly influence the onset and/or outcome of autoimmune diseases. Until now, there is only limited information on the antigen-specific balance between proinflammatory and regulatory responses in humans. Here we analyzed the natural immune response against a candidate autoantigen in rheumatoid arthritis, human cartilage glycoprotein-39 (HC gp-39).