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. 2024 Sep;54(9):e2350716.
doi: 10.1002/eji.202350716. Epub 2024 Jun 5.

IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent

Maria R Encarnacion-Garcia #  1 , Raúl De la Torre-Baez #  1 , María A Hernandez-Cueto #  2 , Laura A Velázquez-Villegas  3 , Aurora Candelario-Martinez  1 , Ana Beatriz Sánchez-Argáez  4 , Perla H Horta-López  1 , Armando Montoya-García  4 , Gustavo Alberto Jaimes-Ortega  5   6 , Luis Lopez-Bailon  7 , Zayda Piedra-Quintero  4 , Gabriela Carrasco-Torres  8 , Marlon De Ita  9   10 , María Del Pilar Figueroa-Corona  4 , José Esteban Muñoz-Medina  2 , Magdalena Sánchez-Uribe  11 , Arturo Ortiz-Fernández  12 , Marco Antonio Meraz-Ríos  4 , Angélica Silva-Olivares  13 , Abigail Betanzos  13 , Guillermina Juliana Baay-Guzman  14 , Fernando Navarro-Garcia  12 , Saúl Villa-Treviño  12 , Francisco Garcia-Sierra  12 , Bulmaro Cisneros  9 , Michael Schnoor  4 , Vianney F Ortíz-Navarrete  4 , Nicolás Villegas-Sepúlveda  4 , Ricardo Valle-Rios  5   15 , Oscar Medina-Contreras  16 , Lilia G Noriega  3 , Porfirio Nava  1
Affiliations
Free article

IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent

Maria R Encarnacion-Garcia et al. Eur J Immunol. 2024 Sep.
Free article

Abstract

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-γ 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-γ 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-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.

Keywords: Interferon‐γ; Mitochondria; Necroptosis; Paneth cells; ROS; mTORC1.

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