Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics
Juana Serrano-Lopez,
Shailaja Hegde,
Sachin Kumar,
Josefina Serrano,
Jing Fang,
Ashley M Wellendorf,
Paul A Roche,
Yamileth Rangel,
Leolene J Carrington,
Hartmut Geiger,
H Leighton Grimes,
Sanjiv Luther,
Ivan Maillard,
Joaquin Sanchez-Garcia,
Daniel T Starczynowski,
Jose A Cancelas
Affiliations
Juana Serrano-Lopez
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States
Shailaja Hegde
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States; Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, United States
Sachin Kumar
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States
Josefina Serrano
Hematology Department, Reina Sofía University Hospital/Maimonides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba, Córdoba, Spain
Jing Fang
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States
Ashley M Wellendorf
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States
Paul A Roche
Center for Cancer Research, National Cancer Institute, Bethesda, United States; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States
Yamileth Rangel
Hematology Department, Reina Sofía University Hospital/Maimonides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba, Córdoba, Spain
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States; Institute of Molecular Medicine, Ulm University, Ulm, Germany
H Leighton Grimes
Immunobiology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States
Sanjiv Luther
Center for Immunity and Infection, Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
Ivan Maillard
University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
Joaquin Sanchez-Garcia
Hematology Department, Reina Sofía University Hospital/Maimonides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba, Córdoba, Spain
Daniel T Starczynowski
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States; Department of Cancer Biology, University of Cincinnati, Cincinnati, United States
Divisions of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States; Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, United States
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 NF-κB independent, Traf6/IκB-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 and upregulation of BM myeloid progenitor Ccr7 signaling. Mature myeloid Traf6 signaling is anti-inflammatory and necessary for lymph node 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.
