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Retinoic acid signaling in thymic epithelial cells regulates thymopoiesis

Wendland, Kerstin LU ; Niss, Kristoffer; Kotarsky, Knut LU ; Wu, Nikita Y.H.; White, Andrea J.; Jendholm, Johan LU ; Rivollier, Aymeric LU ; Izarzugaza, Jose M.G.; Brunak, Søren and Holländer, Georg A., et al. (2018) In Journal of Immunology 201(2). p.524-532
Abstract

Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis. In the absence of RA signaling in TEC, cortical TEC (cTEC) and CD80loMHC class IIlo medullary TEC displayed subset-specific alterations in gene expression, which in cTEC included genes involved in epithelial proliferation, development, and differentiation. Mice whose TEC were unable to respond to RA showed increased cTEC proliferation, an accumulation of stem cell Ag-1hi cTEC, and, in early life, a decrease in medullary TEC... (More)

Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis. In the absence of RA signaling in TEC, cortical TEC (cTEC) and CD80loMHC class IIlo medullary TEC displayed subset-specific alterations in gene expression, which in cTEC included genes involved in epithelial proliferation, development, and differentiation. Mice whose TEC were unable to respond to RA showed increased cTEC proliferation, an accumulation of stem cell Ag-1hi cTEC, and, in early life, a decrease in medullary TEC numbers. These alterations resulted in reduced thymic cellularity in early life, a reduction in CD4 single-positive and CD8 single-positive numbers in both young and adult mice, and enhanced peripheral CD8+ T cell survival upon TCR stimulation. Collectively, our results identify RA as a regulator of TEC homeostasis that is essential for TEC function and normal thymopoiesis.

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Journal of Immunology
volume
201
issue
2
pages
9 pages
publisher
American Association of Immunologists
external identifiers
  • scopus:85049869713
ISSN
0022-1767
DOI
10.4049/jimmunol.1800418
language
English
LU publication?
yes
id
937dec18-4b2a-4201-a33c-9d773385c1ec
date added to LUP
2018-07-24 11:52:25
date last changed
2019-02-20 11:22:58
@article{937dec18-4b2a-4201-a33c-9d773385c1ec,
  abstract     = {<p>Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis. In the absence of RA signaling in TEC, cortical TEC (cTEC) and CD80<sup>lo</sup>MHC class II<sup>lo</sup> medullary TEC displayed subset-specific alterations in gene expression, which in cTEC included genes involved in epithelial proliferation, development, and differentiation. Mice whose TEC were unable to respond to RA showed increased cTEC proliferation, an accumulation of stem cell Ag-1<sup>hi</sup> cTEC, and, in early life, a decrease in medullary TEC numbers. These alterations resulted in reduced thymic cellularity in early life, a reduction in CD4 single-positive and CD8 single-positive numbers in both young and adult mice, and enhanced peripheral CD8<sup>+</sup> T cell survival upon TCR stimulation. Collectively, our results identify RA as a regulator of TEC homeostasis that is essential for TEC function and normal thymopoiesis.</p>},
  author       = {Wendland, Kerstin and Niss, Kristoffer and Kotarsky, Knut and Wu, Nikita Y.H. and White, Andrea J. and Jendholm, Johan and Rivollier, Aymeric and Izarzugaza, Jose M.G. and Brunak, Søren and Holländer, Georg A. and Anderson, Graham and Sitnik, Katarzyna M. and Agace, William W.},
  issn         = {0022-1767},
  language     = {eng},
  month        = {07},
  number       = {2},
  pages        = {524--532},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Retinoic acid signaling in thymic epithelial cells regulates thymopoiesis},
  url          = {http://dx.doi.org/10.4049/jimmunol.1800418},
  volume       = {201},
  year         = {2018},
}