Characterization of the thymic IL-7 niche in vivo.

Archive ouverte

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.

Edité par CCSD ; National Academy of Sciences -

International audience. 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion