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.I.* ; Heine, H.* ; Roeder, T.*
Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways.
Cell Rep. 35:108956 (2021)
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.
Impact Factor
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Times Cited
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Cited By
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Drosophila Melanogaster, Asthma, Copd, Toll-like Receptor, Trachea, Tak1, Nf-kappab
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
HGF-Berichtsjahr
2021
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 35,
Heft: 1,
Seiten: ,
Artikelnummer: 108956
Supplement: ,
Reihe
Verlag
Cell Press
Verlagsort
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Allergy
PSP-Element(e)
G-505400-001
Förderungen
Priority Area Asthma & Allergy, Research Center Borstel
Leibniz Science Campus Evolung
Cluster of Excellence "PMI''
Cluster of Excellence "Inflammation@interfaces''
Deutsche Forschungsgemeinschaft (DFG), Germany
Copyright
Erfassungsdatum
2021-05-28