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 language | English (US) |
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Pages (from-to) | 1453-1466.e4 |
Journal | Immunity |
Volume | 50 |
Issue number | 6 |
DOIs | |
State | Published - 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