Tissue-autonomous immune response regulates stress signalling during hypertrophy

Abstract
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Abstract

Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via Ras^V12-overexpression in the postmitotic salivary glands of Drosophila larvae, we overrode the glands adaptability to growth signals and induced hypertrophy. The accompanied loss of tissue integrity, recognition by cellular immunity and cell death are all buffered by blocking stress signalling through a genuine tissue-autonomous immune response. This novel, spatio-temporally tightly regulated mechanism relies on the inhibition of a feedback-loop in the JNK-pathway by the immune effector and antimicrobial peptide Drosomycin. While this interaction might allow growing salivary glands to cope with temporary stress, continuous Drosomycin expression in Ras^V12-glands favors unrestricted hypertrophy. These findings indicate the necessity to refine therapeutic approaches that stimulate immune responses by acknowledging their possible, detrimental effects in damaged or stressed tissues.

Data availability

All sequencing data has been deposited at NCBI GEO under the record GSE138936.

The following data sets were generated

(2019) Transcriptomes of whole hypertrophic Drosophila salivary glands and separated proximal gland parts
NCBI Gene Expression Omnibus, GSE138936.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138936

Article and author information

Author details

Robert Krautz

Department of Biology, University of Copenhagen, Copenhagen, Denmark

For correspondence
rkrautz@binf.ku.dk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0457-1348
Dilan Khalili

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9785-9641
Ulrich Theopold

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden

For correspondence
uli.theopold@su.se

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1009-8254

Funding

Vetenskapsrådet (VR-2010-5988)

Ulrich Theopold

Vetenskapsrådet (VR 2016-04077)

Ulrich Theopold

Swedish Cancer Foundation (CAN 2010/553)

Ulrich Theopold

Swedish Cancer Foundation (CAN 2013/546)

Ulrich Theopold

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.