title: Lymphotoxin-β receptor signaling through NF-κB2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells.
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.
authors.affiliation: School of Immunity and Infection, IBR-MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, UK. c.benezech@bham.ac.uk
authors.forename: Cécile
authors.initials: C
authors.lastname: Bénézech
authors.forename: Emma
authors.initials: E
authors.lastname: Mader
authors.forename: Guillaume
authors.initials: G
authors.lastname: Desanti
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Andrea
authors.initials: A
authors.lastname: White
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Caamaño
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D008198:Lymph Nodes / Q000276:immunology*; D053259:Lymphotoxin beta Receptor / Q000276:immunology; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D017154:Stromal Cells / Q000276:immunology; D051841:Transcription Factor RelB / Q000276:immunology / Q000378:metabolism
chemical_list: D053259:Lymphotoxin beta Receptor; D052003:NF-kappa B p52 Subunit; C497594:Relb protein, mouse; D051841:Transcription Factor RelB