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

doi:10.1016/j.celrep.2021.108956

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 SilvermanHarald Renz, Petra Pfefferle, Holger Heine, Thomas Roeder^*

^*Corresponding author for this work

Institute of Anatomy

12 Citations (Scopus)

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.

Original language	English
Article number	108956
Journal	Cell Reports
Volume	35
Issue number	1
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2021.108956
Publication status	Published - 06.04.2021

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

204-05 Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2021.108956

Cite this

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., ... Roeder, T. (2021). Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways. Cell Reports, 35(1), Article 108956. https://doi.org/10.1016/j.celrep.2021.108956

@article{0c310ff59c0b43d5ac39849bd5207956,

title = "Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways",

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.",

author = "Christina Wagner and Karin Uliczka and Judith Bossen and Xiao Niu and Christine Fink and Marcus Thiedmann and Mirjam Knop and Christina Vock and Ahmed Abdelsadik and Zissler, {Ulrich M.} and Kerstin Isermann and Holger Garn and Mario Pieper and Michael Wegmann and Koczulla, {Andreas R.} and Vogelmeier, {Claus F.} and Schmidt-Weber, {Carsten B.} and Heinz Fehrenbach and Peter K{\"o}nig and Neil Silverman and Harald Renz and Petra Pfefferle and Holger Heine and Thomas Roeder",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = apr,

day = "6",

doi = "10.1016/j.celrep.2021.108956",

language = "English",

volume = "35",

journal = "Cell Reports",

issn = "2211-1247",

number = "1",

}

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 2021, 'Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways', Cell Reports, vol. 35, no. 1, 108956. https://doi.org/10.1016/j.celrep.2021.108956

TY - JOUR

T1 - Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways

AU - Wagner, Christina

AU - Uliczka, Karin

AU - Bossen, Judith

AU - Niu, Xiao

AU - Fink, Christine

AU - Thiedmann, Marcus

AU - Knop, Mirjam

AU - Vock, Christina

AU - Abdelsadik, Ahmed

AU - Zissler, Ulrich M.

AU - Isermann, Kerstin

AU - Garn, Holger

AU - Pieper, Mario

AU - Wegmann, Michael

AU - Koczulla, Andreas R.

AU - Vogelmeier, Claus F.

AU - Schmidt-Weber, Carsten B.

AU - Fehrenbach, Heinz

AU - König, Peter

AU - Silverman, Neil

AU - Renz, Harald

AU - Pfefferle, Petra

AU - Heine, Holger

AU - Roeder, Thomas

PY - 2021/4/6

Y1 - 2021/4/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85103777912&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.108956

DO - 10.1016/j.celrep.2021.108956

M3 - Journal articles

C2 - 33826881

AN - SCOPUS:85103777912

SN - 2211-1247

VL - 35

JO - Cell Reports

JF - Cell Reports

IS - 1

M1 - 108956

ER -

Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this