Gut microbial composition modulates food-specific CD4+ T cells in food allergy 2256989

Abstract Introduction The growing food allergy epidemic is thought to be related to changing environmental factors, particularly changes in the gut microbiome. While prior work has demonstrated that food allergy can be modulated by gut microbes, little is known about how food allergen-specific CD4+ T cells are affected by gut microbial composition. Here, we report that food allergy severity differs between mice obtained from two different specific pathogen-free vendors (Jackson Labs [Jax] and Taconic Biosciences [Tac]) along with differences in food-allergen specific Treg cells in the small intestine. Methods Mice were sensitized to ovalbumin (OVA) via intraperitoneal injection of OVA with alum. Two weeks later, animals were challenged with 3-7 gavages of OVA. Animals were observed for development of diarrhea within 60 minutes following challenge. Body temperature was tracked before and after gavage. Lymphocytes were isolated from small intestine lamina propria (SI LP) and stained with OVA peptide:MHCII tetramers or for markers of mucosal mast cells (MMC). Intestinal permeability was measured in naive Tac and Jax animals using FITC-dextran uptake assay. In co-housing experiments, mice were co-housed for 4 weeks prior to OVA sensitization. Results Mice from Tac developed diarrhea and anaphylaxis after fewer allergen exposures than mice from Jax. We also found that Tac mice have significantly fewer allergen-specific regulatory T cells in SI LP compared to mice from Jax. In addition, Tac mice had a greater abundance of MMCs and increased intestinal permeability. This increased food allergy severity phenotype was transferable via co-housing, which corresponded to a shift in Jax microbial communities towards those found in Tac mice. Conclusion Our findings demonstrate for the first time that food allergen-specific Treg cells can be modulated by gut microbial community composition, which in turn is correlated to food allergy severity. Altered intestinal permeability may be a mechanism behind this relationship. Funding Source Life Science Research Association Topic Categories Mucosal and Regional Immunology (MUC)