Characterization of the thymic IL-7 niche in vivo
Open Access
- 3 February 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (5), 1512-1517
- https://doi.org/10.1073/pnas.0809559106
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-7hi cells). IL-7hi 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-7hi cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7hi 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.Keywords
This publication has 36 references indexed in Scilit:
- Impact of niche aging on thymic regeneration and immune reconstitutionSeminars in Immunology, 2007
- Analysis of thymic stromal cell populations using flow cytometryJournal of Immunological Methods, 2002
- Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral selfNature Immunology, 2001
- Lymphostromal interactions in thymic development and functionNature Reviews Immunology, 2001
- Increased production of IL-7 accompanies HIV-1–mediated T-cell depletion: implications for T-cell homeostasisNature Medicine, 2001
- Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine.The Journal of Experimental Medicine, 1995
- Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice.The Journal of Experimental Medicine, 1994
- A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells.1994
- Cell kinetics in the fetal mouse thymus: precursor cell input, proliferation, and emigration.The Journal of Immunology, 1987