Immunosurveillance by Hematopoietic Progenitor Cells Trafficking Through Blood, Lymph, and Peripheral Tissues

Cell. 2007 Nov 30;131(5):994-1008. doi: 10.1016/j.cell.2007.09.047.

Abstract

Constitutive egress of bone marrow (BM)-resident hematopoietic stem and progenitor cells (HSPCs) into the blood is a well-established phenomenon, but the ultimate fate and functional relevance of circulating HSPCs is largely unknown. We show that mouse thoracic duct (TD) lymph contains HSPCs that possess short- and long-term multilineage reconstitution capacity. TD-derived HSPCs originate in the BM, enter the blood, and traffic to multiple peripheral organs, where they reside for at least 36 hr before entering draining lymphatics to return to the blood and, eventually, the BM. HSPC egress from extramedullary tissues into lymph depends on sphingosine-1-phosphate receptors. Migratory HSPCs proliferate within extramedullary tissues and give rise to tissue-resident myeloid cells, preferentially dendritic cells. HSPC differentiation is amplified upon exposure to Toll-like receptor agonists. Thus, HSPCs can survey peripheral organs and can foster the local production of tissue-resident innate immune cells under both steady-state conditions and in response to inflammatory signals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood*
  • Cell Movement / immunology
  • Cell Movement / physiology*
  • DNA-Binding Proteins / genetics
  • Female
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / physiology*
  • Immunologic Surveillance / physiology*
  • Lymphatic System / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Models, Biological
  • Proto-Oncogene Proteins c-kit / genetics
  • Receptors, Lysosphingolipid / genetics
  • Receptors, Lysosphingolipid / physiology
  • Thoracic Duct / immunology
  • Thoracic Duct / metabolism

Substances

  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Receptors, Lysosphingolipid
  • Proto-Oncogene Proteins c-kit