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Immunity. 2019 Jun 18;50(6):1453-1466.e4. doi: 10.1016/j.immuni.2019.04.002. Epub 2019 Apr 30.

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

Author information

1
Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
2
Institute of Systems Immunology, University of Würzburg, 97078 Würzburg, Germany.
3
Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
4
Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France. Electronic address: bajenoff@ciml.univ-mrs.fr.

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.

KEYWORDS:

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

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