Project description:The interplay between the intestinal microbiota and host is critical to intestinal ontogeny and homeostasis. MicroRNAs (miRNAs) may be an underlying link. Intestinal miRNAs are microbiota-dependent and when shed in the lumen, affect resident microorganisms. Yet, longitudinal relationships between intestinal tissue miRNAs, luminal miRNAs, and luminal microorganisms have not been elucidated, especially in early life. Here, we investigated the postnatal cecal miRNA and microbiota populations, their relationship, and their impact on intestinal maturation in specific and opportunistic pathogen free mice; we also assessed if they can be modified by an intervention with allochthonous probiotic lactobacilli. We report that cecal and cecal content miRNA and microbiota signatures are temporally regulated, correlated, and modifiable by probiotics with implications for intestinal maturation. These findings help with understanding causal relationships within the gut ecosystem and provide a basis for preventing and managing their alterations in diseases throughout life.
Project description:Shrimp allergy is the second most common food allergy in the United States. γδ T cells play a regulatory role in peanut immunotherapy, but their role in shrimp allergy remains unclear. We hypothesized γδ T cells play a regulatory role in shrimp allergic disease. We performed single cell RNA sequencing on peripheral cells from shrimp allergic (SA) and healthy control (HC) subjects after stimulation with shrimp tropomyosin. We found significant expansion of γδ T cells and three distinct clusters. One γδ T cell cluster predominated in SA, characterized as CD8+ with a cytotoxic expression profile. We found significant upregulation of TGF-β1 and downregulation of IL-7R in SA-stimulated vs. HC-stimulated γδ T cells, and IL-10 secretion in stimulated SA γδ T cells. γδ T cells play an important role in the pathogenesis of shrimp allergy through lymphocyte-mediated cytotoxin signaling and cytokine-mediated signaling pathways, including TGFβ-1, IL7/TSLP-IL7R, and IL10-IL10R pathways.