Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 46, Issue 4, Pages 846-856Publisher
WILEY
DOI: 10.1002/eji.201545995
Keywords
beta 5t; Development; Epithelial cell; Medulla; Thymic progenitor cell
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Funding
- Swiss National Science Foundation [3100-68310.02, 3100-122558]
- Wellcome Trust [105045/Z/14/Z]
- Medical Research Council [MC_U137761446, MC_UU_12021/1] Funding Source: researchfish
- MRC [MC_U137761446, MC_UU_12021/1] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [24111004, 24111001, 15K19130, 16H02630] Funding Source: KAKEN
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Intrathymic T-cell development is critically dependent on cortical and medullary thymic epithelial cells (TECs). Both epithelial subsets originate during early thymus organogenesis from progenitor cells that express the thymoproteasome subunit eta 5t, a typical feature of cortical TECs. Using in vivo lineage fate mapping, we demonstrate in mice that beta 5t(+) TEC progenitors give rise to the medullary TEC compartment early in life but significantly limit their contribution once the medulla has completely formed. Lineage-tracing studies at single cell resolution demonstrate for young mice that the postnatal medulla is expanded from individual beta 5t(+) cortical progenitors located at the cortico-medullary junction. These results therefore not only define a developmental window during which the expansion of medulla is efficiently enabled by progenitors resident in the thymic cortex, but also reveal the spatio-temporal dynamics that control the growth of the thymic medulla.
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