Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 5, Pages 1512-1517Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0809559106
Keywords
aging; development; thymic epithelial cells; thymus; cytokine
Categories
Funding
- Institut Pasteur
- INSERM
- Ligue Nationale Contre le Cancer (Equipe Labellisee)
- European Molecular Biology Organization
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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-7(hi) cells). IL-7(hi) TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (Ccl19, Ccl25, Cxcl12) and cytokines (Il15) that are critical for normal thymopoiesis. In the adult thymus, IL-7(hi) cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7(hi) 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.
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