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IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent
Maria R Encarnacion-Garcia1, Raúl De la Torre-Baez1, María A Hernandez-Cueto2
1Departament of Physiology, Biophysics, and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico City, Mexico.
European Journal of Immunology
|June 5, 2024
Summary
Interferon-gamma (IFN-γ) disrupts gut homeostasis by stimulating Paneth cell secretion. This process involves mitochondrial activity, ROS production, and is dependent on mTORC1 and necroptosis, revealing a novel role for IFN-γ in regulating intestinal epithelial cells.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Intestinal epithelial cells (IECs) are crucial for gut homeostasis.
- Immune mediators, including interferon-gamma (IFN-γ), influence IEC function.
- The precise mechanisms by which IFN-γ disrupts intestinal epithelial homeostasis are not fully understood.
Purpose of the Study:
- To elucidate the role of IFN-γ in regulating Paneth and Paneth-like cells.
- To investigate the molecular mechanisms by which IFN-γ affects intestinal epithelial homeostasis.
Main Methods:
- In vivo and in vitro experimental models were utilized.
- Analysis of mitochondrial activity, reactive oxygen species (ROS) production, and Paneth cell secretion was performed.
- Investigated the involvement of mTORC1 and necroptosis pathways.
Main Results:
- IFN-γ is spontaneously secreted in the small intestine.
- IFN-γ stimulates mitochondrial activity, ROS production, and Paneth/Paneth-like cell secretion.
- Paneth cell secretion induced by IFN-γ is dependent on mTORC1 and necroptosis.
Conclusions:
- IFN-γ plays a significant role in regulating Paneth cell function.
- The findings reveal a novel mechanism by which IFN-γ contributes to intestinal epithelial homeostasis disruption.
- IFN-γ's pleiotropic functions extend to the regulation of Paneth cell activity in the gut.
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