Retinoic acid signaling in thymic epithelial cells regulates thymopoiesis

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Retinoic acid signaling in thymic epithelial cells regulates thymopoiesis. / Wendland, Kerstin; Niss, Kristoffer; Kotarsky, Knut; Wu, Nikita Y.H.; White, Andrea J.; Jendholm, Johan; Rivollier, Aymeric; Izarzugaza, Jose M.G.; Brunak, Søren; Holländer, Georg A.; Anderson, Graham; Sitnik, Katarzyna M.; Agace, William W.

I: Journal of Immunology, Vol. 201, Nr. 2, 15.07.2018, s. 524-532.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Wendland, K, Niss, K, Kotarsky, K, Wu, NYH, White, AJ, 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, vol. 201, nr. 2, s. 524-532. https://doi.org/10.4049/jimmunol.1800418

APA

CBE

Wendland K, Niss K, Kotarsky K, Wu NYH, White AJ, 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. 201(2):524-532. https://doi.org/10.4049/jimmunol.1800418

MLA

Vancouver

Author

Wendland, Kerstin ; Niss, Kristoffer ; Kotarsky, Knut ; Wu, Nikita Y.H. ; White, Andrea J. ; 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. I: Journal of Immunology. 2018 ; Vol. 201, Nr. 2. s. 524-532.

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 J.

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.

PY - 2018/7/15

Y1 - 2018/7/15

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

VL - 201

SP - 524

EP - 532

JO - Journal of immunology (Baltimore, Md. : 1950)

T2 - Journal of immunology (Baltimore, Md. : 1950)

JF - Journal of immunology (Baltimore, Md. : 1950)

SN - 1550-6606

IS - 2

ER -