Barley based gluten free beer - a blessing or an uncontrollable risk?

Recent reports have highlighted that beer labelled "gluten-free", crafted with enzymatic treatments to remove gluten, may contain polypeptides that could be immunotoxic to individuals with coeliac disease. As strict adherence to a gluten-free diet is the only way to manage this condition, accurate labelling is crucial to those with coeliac disease. This paper aims to discuss the presence, levels and immunogenicity of gluten peptides found in gluten-reduced barley beers. While advances have been made in the detection and quantification of gluten peptides in beer, there are still challenges to the interpretation of gluten measurements as well as to assess whether peptides are immunotoxic in vivo. To make progress, future efforts should involve a combination of in vivo toxicity assessment of the degraded proteins, development of standardised gluten-free production strategies to minimise variability in gluten fragment presence, guidance on how to control the outcome as well as to develop appropriate reference materials and calibrators.

Fusarium mycotoxin enniatin B: Cytotoxic effects and changes in gene expression profile.

The mycotoxin enniatin B, a cyclic hexadepsipeptide produced by the plant pathogen Fusarium, is prevalent in grains and grain-based products in different geographical areas. Although enniatins have not been associated with toxic outbreaks, they have caused toxicity in vitro in several cell lines. In this study, the cytotoxic effects of enniatin B were assessed in relation to cellular energy metabolism, cell proliferation, and the induction of apoptosis in Balb 3T3 and HepG2 cells. The mechanism of toxicity was examined by means of whole genome expression profiling of exposed rat primary hepatocytes. Enniatin B altered cellular energy metabolism and reduced cell proliferation in Balb 3T3 and HepG2 cell lines. Furthermore, the proportion of apoptotic cell populations of Balb 3T3 cells slightly increased. On the other hand, enniatin B caused necrotic cell death in primary hepatocytes. Gene expression studies revealed the alteration of energy metabolism due to effects on mitochondrial organization and function and the assembly of complex I of the electron transport chain.

Invariant Natural Killer T Cells Play a Role in Chemotaxis, Complement Activation and Mucus Production in a Mouse Model of Airway Hyperreactivity and Inflammation.

CD1d-restricted invariant natural killer T (iNKT) cells play a critical role in the induction of airway hyperreactivity (AHR). After intranasal alpha-galactosylceramide (α-GalCer) administration, bronchoalveolar lavage fluid (BALF) proteins from mouse lung were resolved by two-dimensional differential gel electrophoresis (2D-DIGE), and identified by tandem mass spectroscopy. A lack of iNKT cells prevented the development of airway responses including AHR, neutrophilia and the production of the proinflammatory cytokines in lungs. Differentially abundant proteins in the BALF proteome of α-GalCer-treated wild type mice included lungkine (CXCL15), pulmonary surfactant-associated protein D (SFTPD), calcium-activated chloride channel regulator 1 (CLCA1), fragments of complement 3, chitinase 3-like proteins 1 (CH3LI) and 3 (CH3L3) and neutrophil gelatinase-associated lipocalin (NGAL). These proteins may contribute to iNKT regulated AHR via several mechanisms: altering leukocyte chemotaxis, increasing airway mucus production and possibly via complement activation.

Activating NK-cell receptors co-stimulate CD4(+)CD28(-) T cells in patients with rheumatoid arthritis.

Effector T-cell responses can be modulated by competing positive or negative signals transduced by NK-cell receptors (NKR). In the CD4(+) T-cell population, the expression of NKR is primarily found in the CD4(+)CD28(-) T-cell subset, also known as CD28(null) T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR-expressing CD4(+)CD28(-) T cells in patients with RA. By analyzing a broad array of NKR on CD4(+)CD28(-) T cells we found a significant expression of the co-activating receptors 2B4 (CD244), DNAM-1 (CD226), and CRACC. Pair-wise ligations of 2B4 with DNAM-1 and/or NKG2D lead to increased effector functions of primary CD4(+)CD28(-) T cells to suboptimal levels of anti-CD3 stimulation. Using multi-parameter flow cytometry, we demonstrate that such co-ligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR-mediated functional modulation of CD4(+)CD28(-) T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.

Smad3 signal transducer regulates skin inflammation and specific IgE response in murine model of atopic dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by itchy, dry, and inflamed skin. Transforming growth factor (TGF)-beta is an important fibrogenic and immunomodulatory factor that regulates cellular processes in the injured and inflamed skin. This study examines the role of the TGF-beta-Smad signaling pathway using Smad3-deficient mice in a murine model of AD. Dermatitis was induced in mice by epicutaneous application of ovalbumin (OVA) applied in a patch to tape-stripped skin. OVA-specific IgE and IgG2a antibody levels were measured by ELISA. Skin biopsies from sensitized skin areas were used for RNA isolation, histology, and immunohistochemical examination. The thickness of dermis was significantly reduced in OVA-sensitized skin of Smad3-/- mice. The defect in the dermal thickness was accompanied by a decrease in the expression of mRNA for proinflammatory cytokines IL-6 and IL-1beta in the OVA-sensitized skin. In contrast, the number of mast cells was significantly increased in OVA-sensitized skin of Smad3-/- mice, which also exhibited elevated levels of OVA-specific IgE. These results demonstrate that the Smad3-pathway regulates allergen-induced skin inflammation and systemic IgE antibody production in a murine model AD. The Smad3 signaling pathway might be a potential target in the therapy of allergic skin diseases.