Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis. / Wendland, Kerstin; Niss, Kristoffer; Kotarsky, Knut; Wu, Nikita Yeuk Hung; White, Andrea J.; Jendholm, Lars Johan; Rivollier, Aymeric; Izarzugaza, Jose M.G.; Brunak, Søren; Holländer, Georg A; Anderson, Graham; Sitnik, Katarzyna M.; Agace, William W.
In: Journal of Immunology, Vol. 201, No. 2, 2018, p. 524-532.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis
AU - Wendland, Kerstin
AU - Niss, Kristoffer
AU - Kotarsky, Knut
AU - Wu, Nikita Yeuk Hung
AU - White, Andrea J.
AU - Jendholm, Lars Johan
AU - Rivollier, Aymeric
AU - Izarzugaza, Jose M.G.
AU - Brunak, Søren
AU - Holländer, Georg A
AU - Anderson, Graham
AU - Sitnik, Katarzyna M.
AU - Agace, William W.
N1 - Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.4049/jimmunol.1800418
DO - 10.4049/jimmunol.1800418
M3 - Journal article
C2 - 29848752
VL - 201
SP - 524
EP - 532
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -
ID: 197765994