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Proceedings of the National Academy of Sciences of the United States of AmericaVolume 106, Issue 5, 3 February 2009, Pages 1512-1517

Characterization of the thymic IL-7 niche in vivo(Article)(Open Access)

  • Alves, N.L.,
  • Goff, O.R.-L.,
  • Huntington, N.D.,
  • Sousa, A.P.,
  • Ribeiro, V.S.G.,
  • Bordack, A.,
  • Vives, F.L.,
  • Peduto, L.,
  • Chidgey, A.,
  • Cumano, A.,
  • Boyd, R.,
  • Eberl, G.,
  • Di Santo, J.P.
  • View Correspondence (jump link)
  • aCytokines and Lymphoid Development Unit, Institut Pasteur, Paris, France
  • bLymphocyte Development Unit, Institut Pasteur, Paris, France
  • cPlate-Forme Technologique Centre d'Ingénierie Géné tique Murine, Institut Pasteur, Paris, France
  • dLaboratory of Lymphoid Tissue Development, Institut Pasteur, Paris, France
  • eINSERM U668, Paris, France
  • fMonash Immunology and Stem Cell Laboratories (MISCL), Monash University, VIC 3800, Australia

Abstract

The thymus represents the "cradle" for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the ''environmental niche'' of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of Il7 transcripts (IL-7hi cells). IL-7hi TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (Ccl19, Ccl25, Cxcl12) and cytokines (II15) that are critical for normal thymopoiesis. In the adult thymus, IL-7hi cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7hi cells decreases with age, suggesting a mechanism for the age-related thymic involution that is associated with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated under distinct physiological conditions. This IL-7 reporter mouse provides a valuable tool to further dissect the mechanisms that govern thymic IL-7 expression in vivo. © 2009 by The National Academy of Sciences of the USA.

Author keywords

AgingCytokineDevelopmentThymic epithelial cellsThymus

Indexed keywords

EMTREE drug terms:interleukin 15interleukin 7macrophage inflammatory protein 3betastromal cell derived factor 1interleukin 7messenger RNAphotoproteinyellow fluorescent protein, mouse
EMTREE medical terms:animal experimentarticleC57BL 6 mousecell junctioncell maturationcellular distributioncontrolled studyepithelium cellfetus developmentgene expressionin vivo studyinvolutionmousenonhumanpriority journalprotein analysisprotein expressionprotein localizationT lymphocytethymustransgenic mouseanimalbacterial artificial chromosomecell culturecytologyepithelium cellgeneticsimmunologymetabolismpolymerase chain reactionreporter gene
Species Index:Bacteria (microorganisms)Mus musculus
MeSH:AnimalsCells, CulturedChromosomes, Artificial, BacterialEpithelial CellsGenes, ReporterInterleukin-7Luminescent ProteinsMiceMice, TransgenicPolymerase Chain ReactionRNA, MessengerThymus Gland

Chemicals and CAS Registry Numbers:

macrophage inflammatory protein 3beta, 181030-14-8;

Interleukin-7; Luminescent Proteins; RNA, Messenger; yellow fluorescent protein, mouse

  • ISSN: 00278424
  • CODEN: PNASA
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1073/pnas.0809559106
  • PubMed ID: 19164539
  • Document Type: Article

  Di Santo, J. P.; Cytokines and Lymphoid Development Unit, Institut Pasteur, France;
© Copyright 2009 Elsevier B.V., All rights reserved.

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