Lymphatic Endothelial Cells Are Essential Components of the Subcapsular Sinus Macrophage Niche

Isabelle Mondor, Myriam Baratin, Marine Lagueyrie, Lisa Saro, Sandrine Henri, Rebecca Gentek, Delphine Suerinck, Wolfgang Kastenmuller, Jean X. Jiang, Marc Bajénoff

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

In lymph nodes, subcapsular sinus macrophages (SSMs) form an immunological barrier that monitors lymph drained from peripheral tissues. Upon infection, SSMs activate B and natural killer T (NKT) cells while secreting inflammatory mediators. Here, we investigated the mechanisms regulating development and homeostasis of SSMs. Embryonic SSMs originated from yolk sac hematopoiesis and were replaced by a postnatal wave of bone marrow (BM)-derived monocytes that proliferated to establish the adult SSM network. The SSM network self-maintained by proliferation with minimal BM contribution. Upon pathogen-induced transient deletion, BM-derived cells contributed to restoring the SSM network. Lymphatic endothelial cells (LECs) were the main source of CSF-1 within the lymph node and conditional deletion of Csf1 in adult LECs decreased the network of SSMs and medullary sinus macrophages (MSMs). Thus, SSMs have a dual hematopoietic origin, and LECs are essential to the niche supporting these macrophages. Mondor et al. demonstrate that subcapsular sinus macrophages (SSMs) self-maintain by proliferation in the adult mouse lymph node and that homeostasis of SSMs and medullary sinus macrophages (MSMs) relies on secretion of CSF-1 by neighboring lymphatic endothelial cells (LECs).

Original languageEnglish (US)
Pages (from-to)1453-1466.e4
JournalImmunity
Volume50
Issue number6
DOIs
StatePublished - Jun 18 2019

Keywords

  • colony stimulating factor-1
  • homeostasis
  • lymph node
  • macrophages
  • niche
  • ontogeny
  • stromal cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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