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Wichers, H. J.

Publications and source records attributed to Wichers, H. J..

3 recordsLinked to original sources

Autologous Immune Cell Assay to Investigate risk of Processed- and Novel Food-Induced type 2 Inflammation in Peanut Allergy

Peanut allergy represents a major food-allergy burden, raising concerns about food processing and novel dietary products. Current diagnostics assess primarily allergic endpoints rather than immune mechanisms initiating and maintaining type 2 inflammation, particularly DC2-mediated Th2 polarization. Here, an in vitro autologous monocyte-derived dendritic cell (moDC)-T cell and B cell assay has been established to study immunomodulatory effects induced by unprocessed (P-D) and processed (P-DH (heated) or P-DHG (heated and glycated)) peanut proteins and emerging foods (protein concentrates or whole biomass), related to ex vivo DC2-T cell reactions. CD14+ monocytes, CD4+ T cells and CD19+ B cells were isolated from six peanut-allergic patients PBMCs. MoDCs generated with IL4/GM-CSF were exposed (48h) to type 2 polarizing cytokine (DC2) mix, or DC2 mix combined with the food samples. Next, DC2s were co-cultured with T cells (5d), followed by B cells incubation with DC2/T cell supernatant and food samples (10d). Supernatants and cells were analyzed for Th1/Th2/Th-regulatory (Treg) cells, IgE and IgG profiles. DC2 induced a strong Th2 phenotype and activity, P-D DC2 further enhanced IL13 secretion and %Tregs. P-DH DC2 favored Th2, whereas P-DHG DC2 increased IFN{gamma}, with neither increasing %Treg. All increased CD40L+CD25+ memory Th2 cells. Wheat, whey and seaweed biomass had little effect, whereas algae DC2 showed distinct immunomodulatory, adjuvant-like activity. In conclusion, this autologous in vitro assay captures peanut-specific and generic Th2 responses and reactivity to food samples, supporting its use as additional tool to assess type 2-driving potential and allergenicity of emerging foods and processing methods in peanut-allergic patients. Clinical trial registrationThe current in vitro study was conducted in accordance with the Declaration of Helsinki and approved by the Medical Ethics Review Committee (METC) of the Erasmus MC (NL79534.078.21 MEC-2021-0905) and registrated at International Clinical Trials Registry Platform (NL-OMON51765). Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/705773v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1f42191org.highwire.dtl.DTLVardef@c7e4baorg.highwire.dtl.DTLVardef@1798547org.highwire.dtl.DTLVardef@11d0d96_HPS_FORMAT_FIGEXP M_FIG C_FIG Immune cell illustrations were adapted (1, 2) with permission; permission conveyed through Copyright Clearance Center, Inc. Capsule summaryThe autologous moDC-T cell-B cell in vitro assay may be used to assess whether processing methods or new foods might have intrinsic capacity to affect type 2 inflammation in peanut-allergic patients.

immunology↗

Exercise training at different intensities induces heat stress, disrupts barrier function and alters microbiota in the gut of mice

Exercise is generally beneficial for health but strenuous exercise can have detrimental effects on the gastrointestinal tract. The combination of ischemia and heat shock during exercise is a crucial contributor to intestinal epithelial damage. Growing evidence points towards an important regulatory role of gut microbes in intestinal homeostasis. Here, we characterize and compare the effects of moderate and vigorous exercise training on intestinal epithelial damage, stress response, inflammatory response, and gut microbiota alterations in mice and investigate the mechanisms underlying exercise-induced intestinal injury. Exercise training for six weeks caused heat stress in the intestine, resulting in the disruption of the intestinal epithelial barrier and local inflammation. This was characterized by increased colonic HSP-70 and HSF-1 protein expression, increased epithelial permeability, decreased colonic expression of tight junction proteins ZO-1 and occludin and intestinal morphological changes. Daily moderate exercise training caused hereby more severe injury than vigorous training on alternating days. Furthermore, exercise training altered the gut microbiota profile. The abundance of Lactobacillaceae was reduced, potentially contributing to the deteriorated intestinal status, while the abundance of short-chain fatty acid-producing Lachnospiraceae was increased, especially following vigorous training. This increase in short-chain fatty acid-producing bacteria following vigorous training possibly counteracted the impairment of the intestinal barrier function. In summary, exercise disrupts the intestinal barrier function, with vigorous exercise training with intermittent rest days being less damaging than daily moderate exercise training.

physiology↗

A combined microphysiological-computational omics approach in dietary protein evaluation

The ever-growing world population puts pressure on food security. To tackle this, waste stream proteins and novel protein sources need to be evaluated for nutritional value, which requires information on digesta peptide composition in comparison to established protein sources and coupling to biological parameters. Here, we present a novel combined experimental and computational approach comparing seventeen protein sources with cows whey protein (WPC) as benchmark. In vitro digestion was followed by proteomics analysis and statistical model clustering based on Bayesian Information Criterion. Next, we incorporated functional protein data after evaluating the effects of eighteen protein digests on intestinal barrier integrity, viability, brush border enzyme activity and immune parameters using a bioengineered intestine. Our data show that a holistic approach allows evaluating a dietary proteins potential for delivery of bioactive peptides, where protein source (animal, plant or novel source-derived) does not seem to be the driving force for clustering.

bioengineering↗