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Updated: Jan 13, 2026

An Intravital Microscopy-Based Approach to Assess Intestinal Permeability and Epithelial Cell Shedding Performance

An Intravital Microscopy-Based Approach to Assess Intestinal Permeability and Epithelial Cell Shedding Performance

Published on: December 3, 2020

病原体に対する腸管上皮バリア機能とオートファジー応答を連結するARHGEF2アイソフォームスイッチング

Hans-Christian Reinecker, Shuyuan Chen, Alka Diwaker

Research square

|January 9, 2026

Abstract:

Maintenance of intestinal epithelial integrity is essential for host defence, yet how epithelial junctional scaffolds connect to antimicrobial autophagy remains unclear. Here we show that distinct isoforms of the guanine nucleotide exchange factor GEF-H1 (mouse Arhgef2-207; human ARHGEF2-219) localize to adherens junctions in polarized intestinal epithelial cells through interaction with the adhesion molecule Nectin-3 and the cytoskeletal scaffold Afadin. Conditional deletion of Arhgef2-207 in the intestinal epithelium induces compensatory expression of the shorter Arhgef2-201, leading to loss of barrier integrity, activation of autophagy, and small-intestinal inflammation. In human intestinal organoids, infection with Listeria monocytogenes selectively targets the junction-associated ARHGEF2-219 isoform, triggering an isoform switch to ARHGEF2-201 and induction of autophagy through interaction with STING and LC3. This transition coincides with a loss of Na⁺/K⁺-ATPase and epithelial polarity. Together, these findings identify a pathogen-induced ARHGEF2 isoform switch that links junctional perturbation to autophagy and mucosal immune activation, defining a previously unrecognized pathway by which epithelial cells couple barrier disruption to cell-intrinsic host defence.

キーワード:

ARHGEF2 GEF-H1 isoform switching intestinal epithelial barrier autophagy host defense pathogen infection inflammation polarity loss Nectin-3 Afadin Listeria monocytogenes STING LC3 Na+/K+-ATPase

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Human Colonoid Monolayers to Study Interactions Between Pathogens, Commensals, and Host Intestinal Epithelium

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Investigating Intestinal Barrier Breakdown in Living Organoids

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