Functional and molecular analysis of the epithelial barrier of porcine Peyer's patches follicle-associated epithelium

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Peyer’s patches (PP) of the small intestinal mucosa are responsible for immune surveillance of the intestinal lumen. PP are covered by the follicle associated epithelium (FAE), which has specific barrier properties to avoid excessive contact of immune cells and antigens. This barrier function is provided by tight junction (TJ) proteins, which can be affected by endogenous and exogenous factors, though. During the first funding period, we have characterized the epithelial barrier function of porcine PP, analyzed effects of several compounds including tumor necrosis factor α, quercetin, berberine, and caprate, and further developed cell culture systems and protocols for single cell and signaling analysis. From the current state of the art, a number of new hypotheses and experimental challenges emerged, which will be addressed in the second funding period. A main aspect is the specific susceptibility of PP for foodborne and inflammatory effectors in porcine intestine during different stages of development, and analysis in cell models. Thus in the second funding period, studies will be extended regarding (i) new compounds which are currently discussed in context with (patho)physiology, therapy and prevention (secondary plant compounds including hydroxycinnamic acids and cannabinoids, cytokines), (ii) tissues (age groups of piglets), and (iii) cell models, including co-cultured intestinal cells and the established heterologous expression system Xenopus laevis oocyte for even more detailed molecular studies.This focus will continue to allow a productive, hypothesis-driven approach and will further transfer molecular-functional TJ research to the PP-FAE of this species. Therefore, aims of this project are (i) to analyze mechanisms of barrier strengthening and of perturbation in PP-FAE by a series of presumable barrier effectors, (ii) to focus on the relevance of the effects in different age groups, and (iii) to employ the cell models for further analyses of signaling and TJ protein interaction, in vitro. This study continues and extends the use of a broad spectrum of electrophysiological, molecular and immunohistochemical techniques to identify physiologically and pathophysiologically relevant mechanisms of TJ proteins in porcine PP. The special focus on barrier function and signaling will strengthen and extend the new innovative research field at the interface of pig immunology and epithelial physiology to allow a development of novel potentially therapeutic and preventive strategies.