1. Cancer Biology
  2. Immunology and Inflammation
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Tissue-autonomous immune response regulates stress signalling during hypertrophy

  1. Robert Krautz  Is a corresponding author
  2. Dilan Khalili
  3. Ulrich Theopold  Is a corresponding author
  1. University of Copenhagen, Denmark
  2. Stockholm University, Sweden
Research Article
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Cite this article as: eLife 2020;9:e64919 doi: 10.7554/eLife.64919

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.

The following data sets were generated

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0457-1348
  2. Dilan Khalili

    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9785-9641
  3. 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.
    ORCID icon "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.

Reviewing Editor

  1. Bruno Lemaitre, École Polytechnique Fédérale de Lausanne, Switzerland

Publication history

  1. Received: November 15, 2020
  2. Accepted: December 29, 2020
  3. Accepted Manuscript published: December 30, 2020 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

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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