Cellular and Molecular Gastroenterology and Hepatology · 2023 · 12 citations · 65 references
Life SciencesCell BiologyImmunologyInflammationMucosal ImmunologySignal TransductionEpithelial Barrier FunctionGastrointestinal PathophysiologyGut MicrobiotaInflammatory Bowel DiseaseIntestinal Barrier FunctionMucosal Barrier FunctionGut Epithelial Barrier FunctionInflammatory Bowel Disease PathogenesisInflammatory Bowel Disease PathophysiologyIntestinal Barrier IntegrityIntestinal Epithelial Barrier FunctionLoss-of-function EffectsLoss-of-function VariantsProtein Expression Levels
BACKGROUND & AIMS: Loss-of-function variants in the PTPN2 gene are associated with increased risk of inflammatory bowel disease. We recently showed that Ptpn2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage communication, and modulation of the gut microbiome in mice, restricting expansion of a small intestinal pathobiont associated with inflammatory bowel disease. Here, we aimed to identify how Ptpn2 loss affects ileal IEC subtypes and their function in vivo. METHODS: Constitutive Ptpn2 wild-type, heterozygous, and knockout (KO) mice, as well as mice with inducible deletion of Ptpn2 in IECs, were used in the study. Investigation was performed using imaging techniques, flow cytometry, enteroid culture, and analysis of gene and protein levels of IEC markers. RESULTS: control mice. CONCLUSIONS: Constitutive Ptpn2 deficiency affects Paneth cell viability and compromises Paneth cell-specific antimicrobial peptide production. The observed effects may contribute to the increased susceptibility to intestinal infection and dysbiosis in these mice.
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Fiji: an open-source platform for biological-image analysis
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Toshiro Sato, Johan H. van Es, Hugo J.G. Snippert et al. · Nature · 2010 · 2.5K citations