Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis

Research output: Contribution to journalArticlepeer-review

Standard

Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis. / Wendland, Kerstin; Niss, Kristoffer; Kotarsky, Knut; Wu, Nikita Y. H.; White, Andrea; Jendholm, Johan; Rivollier, Aymeric; Izarzugaza, Jose M. G.; Brunak, Søren; Holländer, Georg A.; Anderson, Graham; Sitnik, Katarzyna M.; Agace, William W.

In: Journal of Immunology, 01.07.2018.

Research output: Contribution to journalArticlepeer-review

Harvard

Wendland, K, Niss, K, Kotarsky, K, Wu, NYH, White, A, Jendholm, J, Rivollier, A, Izarzugaza, JMG, Brunak, S, Holländer, GA, Anderson, G, Sitnik, KM & Agace, WW 2018, 'Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis', Journal of Immunology. https://doi.org/10.4049/jimmunol.1800418

APA

Wendland, K., Niss, K., Kotarsky, K., Wu, N. Y. H., White, A., Jendholm, J., Rivollier, A., Izarzugaza, J. M. G., Brunak, S., Holländer, G. A., Anderson, G., Sitnik, K. M., & Agace, W. W. (2018). Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis. Journal of Immunology. https://doi.org/10.4049/jimmunol.1800418

Vancouver

Author

Wendland, Kerstin ; Niss, Kristoffer ; Kotarsky, Knut ; Wu, Nikita Y. H. ; White, Andrea ; Jendholm, Johan ; Rivollier, Aymeric ; Izarzugaza, Jose M. G. ; Brunak, Søren ; Holländer, Georg A. ; Anderson, Graham ; Sitnik, Katarzyna M. ; Agace, William W. / Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis. In: Journal of Immunology. 2018.

Bibtex

@article{4b8ad6ef1212438ba073d310903cc1a8,
title = "Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis",
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 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.",
author = "Kerstin Wendland and Kristoffer Niss and Knut Kotarsky and Wu, {Nikita Y. H.} and Andrea White and Johan Jendholm and Aymeric Rivollier and Izarzugaza, {Jose M. G.} and S{\o}ren Brunak and Holl{\"a}nder, {Georg A.} and Graham Anderson and Sitnik, {Katarzyna M.} and Agace, {William W.}",
note = "Copyright {\textcopyright} 2018 by The American Association of Immunologists, Inc.",
year = "2018",
month = jul,
day = "1",
doi = "10.4049/jimmunol.1800418",
language = "English",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",

}

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 Y. H.

AU - White, Andrea

AU - Jendholm, 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 - 2018/7/1

Y1 - 2018/7/1

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 - Article

C2 - 29848752

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

ER -