Mesenchymal Cells Regulate Retinoic Acid Receptor-Dependent Cortical Thymic Epithelial Cell Homeostasis.
(2012) In Journal of immunology 188(10). p.4801-4809- Abstract
- The vitamin A metabolite and transcriptional modulator retinoic acid (RA) is recognized as an important regulator of epithelial cell homeostasis in several tissues. Despite the known importance of the epithelial compartment of the thymus in T cell development and selection, the potential role of RA in the regulation of thymic cortical and medullary epithelial cell homeostasis has yet to be addressed. In this study, using fetal thymus organ cultures, we demonstrate that endogenous RA signaling promotes thymic epithelial cell (TEC) cell-cycle exit and restricts TEC cellularity preferentially in the cortical TEC compartment. Combined gene expression, biochemical, and functional analyses identified mesenchymal cells as the major source of RA... (More)
- The vitamin A metabolite and transcriptional modulator retinoic acid (RA) is recognized as an important regulator of epithelial cell homeostasis in several tissues. Despite the known importance of the epithelial compartment of the thymus in T cell development and selection, the potential role of RA in the regulation of thymic cortical and medullary epithelial cell homeostasis has yet to be addressed. In this study, using fetal thymus organ cultures, we demonstrate that endogenous RA signaling promotes thymic epithelial cell (TEC) cell-cycle exit and restricts TEC cellularity preferentially in the cortical TEC compartment. Combined gene expression, biochemical, and functional analyses identified mesenchymal cells as the major source of RA in the embryonic thymus. In reaggregate culture experiments, thymic mesenchyme was required for RA-dependent regulation of TEC expansion, highlighting the importance of mesenchyme-derived RA in modulating TEC turnover. The RA-generating potential of mesenchymal cells was selectively maintained within a discrete Ly51(int)gp38(+) subset of Ly51(+) mesenchyme in the adult thymus, suggesting a continual role for mesenchymal cell-derived RA in postnatal TEC homeostasis. These findings identify RA signaling as a novel mechanism by which thymic mesenchyme influences TEC development. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2519382
- author
- Sitnik, Katarzyna M ; Kotarsky, Knut LU ; White, Andrea J ; Jenkinson, William E ; Anderson, Graham and Agace, William LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of immunology
- volume
- 188
- issue
- 10
- pages
- 4801 - 4809
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000303634300012
- pmid:22504647
- scopus:84861142913
- ISSN
- 1550-6606
- DOI
- 10.4049/jimmunol.1200358
- language
- English
- LU publication?
- yes
- id
- 832e5cec-1079-4991-8237-65aa76024545 (old id 2519382)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22504647?dopt=Abstract
- date added to LUP
- 2016-04-04 09:28:19
- date last changed
- 2022-04-23 20:45:12
@article{832e5cec-1079-4991-8237-65aa76024545, abstract = {{The vitamin A metabolite and transcriptional modulator retinoic acid (RA) is recognized as an important regulator of epithelial cell homeostasis in several tissues. Despite the known importance of the epithelial compartment of the thymus in T cell development and selection, the potential role of RA in the regulation of thymic cortical and medullary epithelial cell homeostasis has yet to be addressed. In this study, using fetal thymus organ cultures, we demonstrate that endogenous RA signaling promotes thymic epithelial cell (TEC) cell-cycle exit and restricts TEC cellularity preferentially in the cortical TEC compartment. Combined gene expression, biochemical, and functional analyses identified mesenchymal cells as the major source of RA in the embryonic thymus. In reaggregate culture experiments, thymic mesenchyme was required for RA-dependent regulation of TEC expansion, highlighting the importance of mesenchyme-derived RA in modulating TEC turnover. The RA-generating potential of mesenchymal cells was selectively maintained within a discrete Ly51(int)gp38(+) subset of Ly51(+) mesenchyme in the adult thymus, suggesting a continual role for mesenchymal cell-derived RA in postnatal TEC homeostasis. These findings identify RA signaling as a novel mechanism by which thymic mesenchyme influences TEC development.}}, author = {{Sitnik, Katarzyna M and Kotarsky, Knut and White, Andrea J and Jenkinson, William E and Anderson, Graham and Agace, William}}, issn = {{1550-6606}}, language = {{eng}}, number = {{10}}, pages = {{4801--4809}}, publisher = {{American Association of Immunologists}}, series = {{Journal of immunology}}, title = {{Mesenchymal Cells Regulate Retinoic Acid Receptor-Dependent Cortical Thymic Epithelial Cell Homeostasis.}}, url = {{http://dx.doi.org/10.4049/jimmunol.1200358}}, doi = {{10.4049/jimmunol.1200358}}, volume = {{188}}, year = {{2012}}, }