1. Stem Cells and Regenerative Medicine
  2. Immunology and Inflammation
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Modulation of occluding junctions alters the hematopoietic niche to trigger immune activation

  1. Rohan J Khadilkar
  2. Wayne Vogl
  3. Katharine Goodwin
  4. Guy Tanentzapf  Is a corresponding author
  1. University of British Columbia, Canada
Research Article
  • Cited 14
  • Views 2,553
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Cite this article as: eLife 2017;6:e28081 doi: 10.7554/eLife.28081

Abstract

Stem cells are regulated by signals from their microenvironment, or niche. During Drosophila hematopoiesis, a niche regulates prohemocytes to control hemocyte production. Immune challenges activate cell-signalling to initiate the cellular and innate immune response. Specifically, certain immune challenges stimulate the niche to produce signals that induce prohemocyte differentiation. However, the mechanisms that promote prohemocyte differentiation subsequent to immune challenges are poorly understood. Here we show that bacterial infection induces the cellular immune response by modulating occluding-junctions at the hematopoietic niche. Occluding-junctions form a permeability barrier that regulates the accessibility of prohemocytes to niche derived signals. The immune response triggered by infection causes barrier breakdown, altering the prohemocyte microenvironment to induce immune cell production. Moreover, genetically induced barrier ablation provides protection against infection by activating the immune response. Our results reveal a novel role for occluding-junctions in regulating niche-hematopoietic progenitor signalling and link this mechanism to immune cell production following infection.

Article and author information

Author details

  1. Rohan J Khadilkar

    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Wayne Vogl

    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Katharine Goodwin

    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Guy Tanentzapf

    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    For correspondence
    tanentz@mail.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2443-233X

Funding

Canadian Institutes of Health Research (G.T.-MOP-272122)

  • Guy Tanentzapf

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

Reviewing Editor

  1. Yukiko M Yamashita, University of Michigan, United States

Publication history

  1. Received: April 25, 2017
  2. Accepted: August 24, 2017
  3. Accepted Manuscript published: August 25, 2017 (version 1)
  4. Version of Record published: September 13, 2017 (version 2)

Copyright

© 2017, Khadilkar 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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