Abstract

Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenesis, and tissue remodeling. Recent reports highlight differential roles for ontogenically distinct renal macrophage populations in disease. However, little is known about how these populations change over time in normal, uninjured kidneys. Prior reports demonstrated a high proportion of HSC-derived macrophages in the young adult kidney. Unexpectedly, using genetic fate-mapping and parabiosis studies, we found that yolk-sac-derived macrophages progressively expand in number with age and become a major contributor to the renal macrophage population in older mice. This chronological shift in macrophage composition involves local cellular proliferation and recruitment from circulating progenitors and may contribute to the distinct immune responses, limited reparative capacity, and increased disease susceptibility of kidneys in the elderly population.

Data availability

All data generated or analyzed during this study are included in the manuscript.

Article and author information

Author details

  1. Shintaro Ide

    Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yasuhito Yahara

    Department of Orthopedic Surgery, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yoshihiko Kobayashi

    Department of Cell Biology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sarah A Strausser

    Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Kana Ide

    Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Anisha Watwe

    Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Shengjie Xu-Vanpala

    Department of Immunology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jamie R Privratsky

    Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Steven D Crowley

    Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Mari L Shinohara

    Department of Immunology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Benjamin A Alman

    Department of Orthopedic Surgery, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Tomokazu Souma

    Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States
    For correspondence
    tomokazu.souma@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3285-8613

Funding

American Society of Nephrology (Career Developmental Grant)

  • Tomokazu Souma

Duke University School of Medicine (Start-up Fund)

  • Tomokazu Souma

National Institute on Aging (R01 AG049745)

  • Benjamin A Alman

National Institute of Allergy and Infectious Diseases (AI088100)

  • Mari L Shinohara

American Heart Association (Postdoctoral fellowship)

  • Shintaro Ide

Kanzawa Medical Research Foundation (Fellowship)

  • Yasuhito Yahara

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

Reviewing Editor

  1. Florent Ginhoux, Agency for Science Technology and Research, Singapore

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were used according to the approved protocols (A051-18-02 and A196-16-0) by the Institutional Animal Care and Use Committee of Duke University.

Version history

  1. Received: September 10, 2019
  2. Accepted: April 16, 2020
  3. Accepted Manuscript published: April 17, 2020 (version 1)
  4. Version of Record published: May 7, 2020 (version 2)

Copyright

© 2020, Ide 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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  1. Shintaro Ide
  2. Yasuhito Yahara
  3. Yoshihiko Kobayashi
  4. Sarah A Strausser
  5. Kana Ide
  6. Anisha Watwe
  7. Shengjie Xu-Vanpala
  8. Jamie R Privratsky
  9. Steven D Crowley
  10. Mari L Shinohara
  11. Benjamin A Alman
  12. Tomokazu Souma
(2020)
Yolk-sac-derived macrophages progressively expand in the mouse kidney with age
eLife 9:e51756.
https://doi.org/10.7554/eLife.51756

Share this article

https://doi.org/10.7554/eLife.51756

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