FoxO factors preserve airway epithelial homeostasis by coordinating adaptive stress responses
Year: 2026
Type: preprint
Abstract: Airway epithelia must maintain functional and structural homeostasis despite exposure to diverse environmental stressors. FoxO transcription factors are well suited to this task, acting as integration hubs that translate extrinsic and intrinsic signals into appropriate physiological responses. We show that FoxO factors in Drosophila, mouse, and human airway epithelial cells (AECs) undergo nuclear translocation in response to stressors including hypoxia, temperature, and oxidative stress. In human airway epithelial cell lines, individual hFOXO factors show distinct, cell-type-specific activation patterns. In Drosophila, hypoxia was the only stressor among those tested that triggered a dfoxo-dependent innate immune response. Because Drosophila possesses a single FoxO ortholog, loss-of-function analysis directly demonstrated that dfoxo is required for stress resistance in the airway epithelium. Reduced FoxO expression was similarly observed in mouse models of asthma and in airway samples from asthma patients, paralleling the increased stress sensitivity seen upon FoxO loss in flies. While our data do not establish that reduced FOXO levels cause asthma, they indicate that FoxO-dependent stress pathways are altered in diseased airways across species. Together, these findings support a model in which FoxO coordinates adaptive epithelial stress responses that maintain airway homeostasis under environmental challenge.
Source: eLife
Authors: Karin Uliczka, Judith Bossen, Ulrich M Zissler, Christine Fink, Xiao Niu, Mario Pieper, Ruben D Prange, Christina Vock, Christina Wagner, Mirjam Knop, Ahmed Abdelsadik, Sören Franzenburg, Iris Bruchhaus, Michael Wegmann, Carsten B Schmidt-Weber, Peter König, Petra Pfefferle, Holger Heine, Thomas Roeder
Institutions: Research Center Borstel - Leibniz Lung Center, German Center for Lung Research, Christian-Albrechts-Universität zu Kiel, Philipps University of Marburg, Universitätsklinikum Gießen und Marburg, Helmholtz Munich, Universities of Giessen and Marburg Lung Center, Rosenheim Technical University of Applied Sciences, Technical University of Munich, University of Lübeck, Aswan University, Bernhard Nocht Institute for Tropical Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W7225820989