Department of Medicine, Division of Infectious Diseases and Immunology
Immunology and Infectious Disease | Respiratory Tract Diseases
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 kappaB (NF-kappaB) 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.
Drosophila melanogaster, asthma, COPD, toll-like receptor, trachea, Tak1, NF-kappaB
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Copyright 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DOI of Published Version
Wagner C, Uliczka K, Bossen J, Niu X, Fink C, Thiedmann M, Knop M, Vock C, Abdelsadik A, Zissler UM, Isermann K, Garn H, Pieper M, Wegmann M, Koczulla AR, Vogelmeier CF, Schmidt-Weber CB, Fehrenbach H, König P, Silverman N, Renz H, Pfefferle P, Heine H, Roeder T. Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways. Cell Rep. 2021 Apr 6;35(1):108956. doi: 10.1016/j.celrep.2021.108956. PMID: 33826881. Link to article on publisher's site
Wagner C, Silverman NS, Roeder T. (2021). Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways. Open Access Publications by UMass Chan Authors. https://doi.org/10.1016/j.celrep.2021.108956. Retrieved from https://escholarship.umassmed.edu/oapubs/4674
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