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Updated: Jun 5, 2026
08:37
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction
Fengjun Wang1, Brad T Schwarz, W Vallen Graham
1State Key Laboratory of Trauma, Burns, and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, China.
Gastroenterology
|October 13, 2006
Summary
Interferon-gamma primes intestinal cells to respond to Tumor Necrosis Factor by increasing TNFR2 expression. This leads to myosin light chain kinase-dependent barrier loss, suggesting TNFR2 blockade may treat intestinal diseases.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Tumor necrosis factor (TNF) is crucial in intestinal diseases.
- TNF disrupts intestinal epithelial barrier function by upregulating myosin light chain kinase (MLCK).
Purpose of the Study:
- To elucidate the signaling pathways through which TNF induces intestinal epithelial barrier loss.
Main Methods:
- Utilized Caco-2 cells and mouse colonocytes for physiologic, morphologic, and biochemical analyses.
- Investigated TNF receptor 1 (TNFR1) and TNFR2 roles in TNF-induced barrier dysfunction.
- Employed in vitro and in vivo models of colitis.
Main Results:
- Interferon-gamma (IFN-γ) pretreatment enhanced TNF-induced barrier dysfunction in Caco-2 cells by increasing MLCK expression and myosin II regulatory light chain (MLC) phosphorylation.
- IFN-γ priming upregulated TNFR1 and TNFR2 expression.
- TNFR2, not TNFR1, was essential for TNF-induced barrier dysfunction; its blockade restored barrier function.
Conclusions:
- IFN-γ primes intestinal epithelia to TNF by inducing TNFR2, mediating MLCK-dependent barrier dysfunction.
- Epithelial TNFR2 blockade presents a potential therapeutic strategy for intestinal diseases.
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