T Cell Zone Resident Macrophages Silently Dispose of Apoptotic Cells in the Lymph Node

Immunity. 2017 Aug 15;47(2):349-362.e5. doi: 10.1016/j.immuni.2017.07.019. Epub 2017 Aug 8.

Abstract

In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1+ MERTK+ cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM-and not DCs-act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner. Furthermore, similar to other macrophages, TZM appear inefficient in priming CD4 T cells. Thus, efferocytosis and T cell activation in the LN are uncoupled processes designated to macrophages and DCs, respectively, with implications to the maintenance of immune homeostasis.

Keywords: dendritic cell; efferocytosis; lymph node; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Apoptosis
  • CD4-Positive T-Lymphocytes / immunology
  • CX3C Chemokine Receptor 1
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Immune Tolerance
  • Lymph Nodes / immunology*
  • Lymphocyte Activation
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phagocytosis*
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Chemokine / metabolism
  • c-Mer Tyrosine Kinase

Substances

  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Proto-Oncogene Proteins
  • Receptors, Chemokine
  • Mertk protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase