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Wagner, C., Uliczka, K., Bossen, J., Niu, X., Fink, C., Thiedmann, M., Knop, M., Vock, C., Abdelsadik, A., Zissler, U.M., Isermann, K., Garn, H., Pieper, M., Wegmann, M., Koczulla, A.R., Vogelmeier, C.F., Schmidt-Weber, C.B., Fehrenbach, H., König, P., Silverman, N., Renz, H., Pfefferle, P., Heine, H., Roeder, T. (2021). Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways.  Cell Rep. 35(1): 108956.
FlyBase ID
FBrf0248634
Publication Type
Research paper
Abstract

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.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Rep.
    Title
    Cell reports
    ISBN/ISSN
    2211-1247
    Data From Reference