Lymphotoxin-β Receptor Signaling through NF-κB2-RelB Pathway Reprograms Adipocyte Precursors as Lymph Node Stromal Cells

Cécile Bénézech, Emma Mader, Guillaume Desanti, Mahmood Khan, Kyoko Nakamura, Andrea White, Carl F Ware, Graham Anderson, Jorge H Caamaño

Research output: Contribution to journalArticlepeer-review

Abstract

Lymph node development during embryogenesis involves lymphotoxin-β receptor engagement and subsequent differentiation of a poorly defined population of mesenchymal cells into lymphoid tissue organizer cells. Here, we showed that embryonic mesenchymal cells with characteristics of adipocyte precursors present in the microenvironment of lymph nodes gave rise to lymph node organizer cells. Signaling through the lymphotoxin-β receptor controlled the fate of adipocyte precursor cells by blocking adipogenesis and instead promoting lymphoid tissue stromal cell differentiation. This effect involved activation of the NF-κB2-RelB signaling pathway and inhibition of the expression of the key adipogenic factors Pparγ and Cebpα. In vivo organogenesis assays show that embryonic and adult adipocyte precursor cells can migrate into newborn lymph nodes and differentiate into a variety of lymph node stromal cells. Thus, we propose that adipose tissues act as a source of lymphoid stroma for lymph nodes and other lymphoid structures associated with fat.
Original languageEnglish
Pages (from-to)721-734
Number of pages14
JournalImmunity
Volume37
Issue number4
DOIs
Publication statusPublished - 19 Oct 2012

Keywords

  • Adipocytes
  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Lymph Nodes
  • Lymphotoxin beta Receptor
  • Mice
  • NF-kappa B p52 Subunit
  • Phenotype
  • Signal Transduction
  • Stromal Cells
  • Transcription Factor RelB

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