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

• Published in: Immunity (Cambridge, Mass.) Vol. 37; no. 4; pp. 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: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.10.2012
• 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
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.06.010

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