1. Immunology and Inflammation
  2. Medicine
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Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics

  1. Juana Serrano-Lopez
  2. Shailaja Hegde
  3. Sachin Kumar
  4. Josefina Serrano
  5. Jing Fang
  6. Ashley M Wellendorf
  7. Paul A Roche
  8. Yamileth Rangel
  9. Leolene J Carrington
  10. Hartmut Geiger
  11. H Leighton Grimes
  12. Sanjiv Luther
  13. Ivan Maillard
  14. Joaquin Sanchez-Garcia
  15. Daniel T Starczynowski
  16. Jose A Cancelas  Is a corresponding author
  1. University of Cincinnati, United States
  2. Hospital Reina Sofia, United States
  3. National Institutes of Health/NCI, United States
  4. Hospital Reina Sofia, Spain
  5. University of Pennsylvania, United States
  6. University of Cincinnati College of Medicine, United States
  7. University of Lausanne, Switzerland
Research Article
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Cite this article as: eLife 2021;10:e66190 doi: 10.7554/eLife.66190

Abstract

Innate immune cellular effectors are actively consumed during systemic inflammation but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to regional lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NFkB independent, Traf6/IkB-kinase/SNAP23 activation dependent, and is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205+/CD172a+ conventional dendritic cells type 2 (cDC2) and upregulation of BM myeloid progenitor Ccr7 signaling. Mature myeloid Traf6 signaling is anti-inflammatory and necessary for lymph node (LN) myeloid cell development. This report unveils the existence and the mechanistic basis of a very early direct traffic of myeloid progenitors from BM to lymphatics during inflammation.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Juana Serrano-Lopez

    Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Shailaja Hegde

    Hoxworth Blood Center, University of Cincinnati, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sachin Kumar

    Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Josefina Serrano

    Hematology, Hospital Reina Sofia, Cordoba, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jing Fang

    Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ashley M Wellendorf

    Hoxworth Blood Center, University of Cincinnati, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Paul A Roche

    Experimental Immunology Branch, National Institutes of Health/NCI, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Yamileth Rangel

    Hematology, Hospital Reina Sofia, Cordoba, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Leolene J Carrington

    Dept. of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7352-3270
  10. Hartmut Geiger

    University of Cincinnati College of Medicine, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5794-5430
  11. H Leighton Grimes

    University of Cincinnati College of Medicine, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Sanjiv Luther

    University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  13. Ivan Maillard

    Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Joaquin Sanchez-Garcia

    Hematology, Hospital Reina Sofia, Cordoba, Spain
    Competing interests
    The authors declare that no competing interests exist.
  15. Daniel T Starczynowski

    University of Cincinnati College of Medicine, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Jose A Cancelas

    Hoxworth Blood Center, University of Cincinnati, Cincinnati, United States
    For correspondence
    jose.cancelas@uc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1291-7233

Funding

National Institutes of Health (GM110628)

  • Jose A Cancelas

National Institutes of Health (DK124115)

  • Jose A Cancelas

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

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 of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol #2019-0041 of Cincinnati Children's Hospital.

Human subjects: Lymphadenopathies from patients were obtained through Institutional Review Board-approved protocols of the Hospital Reina Sofia (Cordoba, Spain), donor informed consent and legal tutor approval in the case of patients younger than 18 years old. Specimens were blindly analyzed through adjudication of unique identifiers.

Reviewing Editor

  1. Cristina Lo Celso, Imperial College London, United Kingdom

Publication history

  1. Received: January 2, 2021
  2. Accepted: April 7, 2021
  3. Accepted Manuscript published: April 8, 2021 (version 1)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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