Characterization of the thymic IL-7 niche in vivo

Nuno L Alves, Odile Richard-Le Goff, Nicholas D Huntington, Ana Patricia Sousa, Vera S G Ribeiro, Allison Bordack, Francina Langa Vives, Lucie Peduto, Ann Patricia Chidgey, Ana Cumano, Richard Lennox Boyd, Gerard Eberl, James P Di Santo

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    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-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.
    Original languageEnglish
    Pages (from-to)1512 - 1517
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume106
    Issue number5
    DOIs
    Publication statusPublished - 2009

    Cite this

    Alves, N. L., Richard-Le Goff, O., Huntington, N. D., Sousa, A. P., Ribeiro, V. S. G., Bordack, A., Vives, F. L., Peduto, L., Chidgey, A. P., Cumano, A., Boyd, R. L., Eberl, G., & Di Santo, J. P. (2009). Characterization of the thymic IL-7 niche in vivo. Proceedings of the National Academy of Sciences of the United States of America, 106(5), 1512 - 1517. https://doi.org/10.1073/pnas.0809559106