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Characterization of the thymic IL-7 niche in vivo

2009; National Academy of Sciences; Volume: 106; Issue: 5 Linguagem: Inglês

10.1073/pnas.0809559106

1091-6490

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

Immune Cell Function and Interaction

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.