IFN-? stimulates Paneth cell secretion through necroptosis mTORC1 dependent
Por:
Encarnacion-Garcia, MR, de la Torre-baez, R, Hernandez-Cueto, MA, Velázquez-Villegas, LA, Candelario-Martinez, A, Sánchez-Argáez, AB, Horta-López, PH, Montoya-Garcia, A, Jaimes-Ortega, GA, Lopez-Bailon, L, Piedra-Quintero, Z, Carrasco-Torres, G, De Ita, M, Figueroa-Corona, MD, Muñoz-Medina, JE, Sánchez-Uribe, M, Ortiz-Fernández, A, Meraz-Ríos, MA, Silva-Olivares, A, Betanzos, A, Baay-Guzman, GJ, Navarro-Garcia, F, Villa-Treviño, S, Garcia-Sierra, F, Cisneros, B, Schnoor, M, Ortíz-Navarrete, VF, Villegas-Sepúlveda, N, Valle-Rios, R, Medina-Contreras, O, Noriega, LG, Nava, P
Publicada:
1 sep 2024
Ahead of Print:
1 jun 2024
Resumen:
Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-gamma a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-gamma is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-gamma, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-gamma also includes the regulation of Paneth cell function in the homeostatic gut.
In PC at the crypt of Lieberk & uuml;hn, IFN-gamma induces mitochondrial activation which causes ROS overproduction and mTORC1 activation. Active mTORC1 produces necroptosis to allow degranulation of PC. The release of the PC intracellular contents stimulates proliferation in neighbored cells. Similar events are triggered in PLC at the bottom of the colonic crypts. image
Filiaciones:
Natl Polytech Inst CINVESTAV IPN, Ctr Res & Adv Studies, Dept Physiol Biophys & Neurosci, San Pedro Zacatenco, Mexico City 07360, Mexico
IMSS, Natl Hosp La Raza Med Ctr, Clin Lab Infectol, Mexico City, Mexico
Natl Inst Hlth Sci & Nutr Salvador Zubiran, Physiol Nutr Dept, Av Vasco Quiroga 15 Col Belisario Dominguez Secc, Mexico City 14080, Mexico
Natl Polytech Inst CINVESTAV IPN, Ctr Res & Adv Studies, Dept Mol Biomed, Mexico City, Mexico
Childrens Hosp Mexico Federico Gomez HIMFG, Immunol & Prote Res Lab, Mexico City, Mexico
Metropolitan Autonomous Univ UAM, Dept Biol & Hlth Sci, Expt Biol Postgrad Program, Mexico City, Mexico
Natl Polytech Inst ENCB IPN, Immunol Dept & Immunol Postgrad Program, Natl Sch Biol Sci, Mexico City, Mexico
Natl Polytech Inst ENCB IPN, Natl Sch Biol Sci, Immunol Postgrad Program, Mexico City, Mexico
Inst Politecn Nacl, CICATA Unidad Morelos, 1036 Z-1,P 2-2, Atlacholoaya 62790, Mexico
Natl Polytech Inst CINVESTAV IPN, Ctr Res & Adv Studies, Dept Genet & Mol Biol, Mexico City, Mexico
UMAE Childrens Hosp, Natl Med Ctr Siglo 21, Med Res Unit Human Genet, Ciudad De Mexico 06720, Mexico
IMSS, Pathol Anat, Specialized Hosp Dr Antonio Fraga Mouret, Natl Hosp La Raza Med Ctr, Ciudad De Mexico, Mexico
Natl Polytech Inst CINVESTAV IPN, Ctr Res & Adv Studies, Dept Cell Biol, Mexico City, Mexico
Natl Polytech Inst CINVESTAV IPN, Ctr Res & Adv Studies, Dept Infectom & Mol Pathogenesis, Mexico City, Mexico
Childrens Hosp Mexico Federico Gomez, Unit Invest Res Oncol Dis, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Childrens Hosp Mexico Federico Gomez UNAM HIMFG, Univ Res Unit, Fac Med,Res Div, Mexico City, Mexico
Childrens Hosp Mexico Federico Gomez, Epidemiol Endocrinol & Nutr Res Unit, Mexico City, Mexico
hybrid, All Open Access
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