Cell Reports (Apr 2021)
Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways
- Christina Wagner,
- Karin Uliczka,
- Judith Bossen,
- Xiao Niu,
- Christine Fink,
- Marcus Thiedmann,
- Mirjam Knop,
- Christina Vock,
- Ahmed Abdelsadik,
- Ulrich M. Zissler,
- Kerstin Isermann,
- Holger Garn,
- Mario Pieper,
- Michael Wegmann,
- Andreas R. Koczulla,
- Claus F. Vogelmeier,
- Carsten B. Schmidt-Weber,
- Heinz Fehrenbach,
- Peter König,
- Neil Silverman,
- Harald Renz,
- Petra Pfefferle,
- Holger Heine,
- Thomas Roeder
Affiliations
- Christina Wagner
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany; Division of Invertebrate Models, Priority Research Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany
- Karin Uliczka
- Division of Invertebrate Models, Priority Research Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany; Division of Innate Immunity, Priority Research Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany
- Judith Bossen
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
- Xiao Niu
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany
- Christine Fink
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany
- Marcus Thiedmann
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany
- Mirjam Knop
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany
- Christina Vock
- Division of Experimental Pneumology, Priority Research Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany
- Ahmed Abdelsadik
- Zoology, Aswan University, Aswan 81528, Egypt; Molecular Biotechnology Program, Faculty of Advanced Basic Sciences, Galala University, 43552 New Galala, Egypt
- Ulrich M. Zissler
- Center of Allergy and Environment (ZAUM), Technical University Munich and Helmholtz Center Munich, German Research Center for Environmental Health, 80802 Munich, Germany; CPC-M, Member of the German Center for Lung Research (DZL), Munich, Germany
- Kerstin Isermann
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany
- Holger Garn
- Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University of Marburg, 35043 Marburg, Germany; UGMLC, Member of the German Center for Lung Research (DZL), Marburg, Germany
- Mario Pieper
- University Lübeck, Anatomical Institute, 23538 Lübeck, Germany
- Michael Wegmann
- Division of Asthma Exacerbation & Regulation, Priority Research Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
- Andreas R. Koczulla
- Pulmonary and Critical Care Medicine, Department of Medicine, Medical Faculty, Philipps University of Marburg, 35043 Marburg, Germany; UGMLC, Member of the German Center for Lung Research (DZL), Marburg, Germany
- Claus F. Vogelmeier
- Pulmonary and Critical Care Medicine, Department of Medicine, Medical Faculty, Philipps University of Marburg, 35043 Marburg, Germany; UGMLC, Member of the German Center for Lung Research (DZL), Marburg, Germany
- Carsten B. Schmidt-Weber
- Center of Allergy and Environment (ZAUM), Technical University Munich and Helmholtz Center Munich, German Research Center for Environmental Health, 80802 Munich, Germany; CPC-M, Member of the German Center for Lung Research (DZL), Munich, Germany
- Heinz Fehrenbach
- Division of Experimental Pneumology, Priority Research Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
- Peter König
- University Lübeck, Anatomical Institute, 23538 Lübeck, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
- Neil Silverman
- University of Massachusetts Medical School, Worcester, MA 01605, USA
- Harald Renz
- Molecular Diagnostics, Institute of Laboratory Medicine and Pathobiochemistry, Medical Faculty, Philipps University of Marburg, 35043 Marburg, Germany; UGMLC, Member of the German Center for Lung Research (DZL), Marburg, Germany
- Petra Pfefferle
- Comprehensive Biobank Marburg, University Medical Center Giessen and Marburg, Medical Faculty, Philipps University Marburg, 35043 Marburg, Germany; UGMLC, Member of the German Center for Lung Research (DZL), Marburg, Germany
- Holger Heine
- Division of Innate Immunity, Priority Research Area Asthma and Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany
- Thomas Roeder
- Zoology, Department of Molecular Physiology, Kiel University, 24118 Kiel, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; Corresponding author
- Journal volume & issue
-
Vol. 35,
no. 1
p. 108956
Abstract
Summary: Extensive remodeling of the airways is a major characteristic of chronic inflammatory lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). To elucidate the importance of a deregulated immune response in the airways for remodeling processes, we established a matching Drosophila model. Here, triggering the Imd (immune deficiency) pathway in tracheal cells induced organ-wide remodeling. This structural remodeling comprises disorganization of epithelial structures and comprehensive epithelial thickening. We show that these structural changes do not depend on the Imd pathway’s canonical branch terminating on nuclear factor κB (NF-κB) activation. Instead, activation of a different segment of the Imd pathway that branches off downstream of Tak1 and comprises activation of c-Jun N-terminal kinase (JNK) and forkhead transcription factor of the O subgroup (FoxO) signaling is necessary and sufficient to mediate the observed structural changes of the airways. Our findings imply that targeting JNK and FoxO signaling in the airways could be a promising strategy to interfere with disease-associated airway remodeling processes.
