Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics
- University of Cincinnati, United States
- Hospital Reina Sofia, United States
- National Institutes of Health/NCI, United States
- Hospital Reina Sofia, Spain
- University of Pennsylvania, United States
- University of Cincinnati College of Medicine, United States
- University of Lausanne, Switzerland
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
Leolene J Carrington
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.
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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Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics
eLife 10:e66190.
https://doi.org/10.7554/eLife.66190
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