UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2021-04-06

Document Type

Article

Disciplines

Immunology and Infectious Disease | Respiratory Tract Diseases

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 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.

Keywords

Drosophila melanogaster, asthma, COPD, toll-like receptor, trachea, Tak1, NF-kappaB

Rights and Permissions

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

10.1016/j.celrep.2021.108956

Source

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

Journal/Book/Conference Title

Cell reports

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33826881

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS