Tissue-autonomous immune response regulates stress signalling during hypertrophy
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 RasV12-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 RasV12-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.
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Transcriptomes of whole hypertrophic Drosophila salivary glands and separated proximal gland partsNCBI Gene Expression Omnibus, GSE138936.
Article and author information
Author details
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
© 2020, Krautz et al.
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.
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