Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 24, Pages 9885-9890Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1301799110
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology
- Japan Society for the Promotion of Science [23249025, 24111004]
- Strategic Japanese-Swiss Cooperative Program on Molecular Medical Research from Japan Science and Technology Agency
- Eidgenossiche Technische Hochschule Zurich
- Grants-in-Aid for Scientific Research [23249025, 24111001, 24111004, 25860361] Funding Source: KAKEN
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The thymus provides multiple microenvironments that are essential for the development and repertoire selection of T lymphocytes. The thymic cortex induces the generation and positive selection of T lymphocytes, whereas the thymic medulla establishes self-tolerance among the positively selected T lymphocytes. Cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs) constitute the major stromal cells that structurally form and functionally characterize the cortex and the medulla, respectively. cTECs and mTECs are both derived from the endodermal epithelium of the third pharyngeal pouch. However, the molecular and cellular characteristics of the progenitor cells for the distinct TEC lineages are unclear. Here we report the preparation and characterization of mice that express the recombinase Cre instead of beta 5t, a proteasome subunit that is abundant in cTECs and not detected in other cell types, including mTECs. By crossing beta 5t-Cre knock-in mice with loxP-dependent GFP reporter mice, we found that beta 5t-Cre-mediated recombination occurs specifically in TECs but not in any other cell types in the mouse. Surprisingly, in addition to cTECs, beta 5t-Cre-loxP-mediated GFP expression was detected in almost all mTECs. These results indicate that the majority of mTECs, including autoimmune regulator-expressing mTECs, are derived from beta 5t-expressing progenitor cells.
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