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Alves, Nuno L.; Richard-Le Goff, Odile; Huntington, Nicholas D.; Sousa, Ana Patricia; Ribeiro, Vera S. G.; Bordack, Allison; Vives, Francina Langa; Peduto, Lucie; Chidgey, Ann; Cumano, Ana; Boyd, Richard; Eberl, Gerard; Di Santo, James P.
Proceedings of the National Academy of Sciences - PNAS, 02/2009, Letnik: 106, Številka: 5Journal Article
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 117 transcripts ${\rm{IL -7}}^{{\rm{hi}}} $. ${\rm{IL - 7}}^{{\rm{hi}}} $ 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, ${\rm{IL - 7}}^{{\rm{hi}}} $ cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of ${\rm{IL - 7}}^{{\rm{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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in: SICRIS
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