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

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 precursor...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2012-10, Vol.37 (4), p.721-734
Main Authors: Bénézech, Cécile, Mader, Emma, Desanti, Guillaume, Khan, Mahmood, Nakamura, Kyoko, White, Andrea, Ware, Carl F., Anderson, Graham, Caamaño, Jorge H.
Format: Article
Language:English
Subjects:
Adipocytes - cytology
Adipocytes - immunology
Animals
Cell Differentiation
Cell Movement
Cells, Cultured
Lymph Nodes - immunology
Lymphotoxin beta Receptor - immunology
Mice
NF-kappa B p52 Subunit - immunology
NF-kappa B p52 Subunit - metabolism
Phenotype
Signal Transduction
Stromal Cells - immunology
Transcription Factor RelB - immunology
Transcription Factor RelB - metabolism
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Summary: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. [Display omitted] ► Adipocyte progenitor cells give rise to lymph node anlage stromal cells ► Adipocyte progenitors’ differentiation is blocked by lymphotoxin-β receptor signaling ► LTβR signaling induces adipocyte progenitor cells to become lymphoid tissue stroma ► Adipocyte progenitor cells support lymphocyte survival ex vivo by expression of IL-7
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2012.06.010