Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis

Research output: Contribution to journalJournal articleResearchpeer-review

  • Kerstin Wendland
  • Niss, Kristoffer
  • Knut Kotarsky
  • Nikita Yeuk Hung Wu
  • Andrea J. White
  • Lars Johan Jendholm
  • Aymeric Rivollier
  • Jose M.G. Izarzugaza
  • Brunak, Søren
  • Georg A Holländer
  • Graham Anderson
  • Katarzyna M. Sitnik
  • William W. Agace

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.

Original languageEnglish
JournalJournal of Immunology
Volume201
Issue number2
Pages (from-to)524-532
Number of pages9
ISSN0022-1767
DOIs
Publication statusPublished - 2018

ID: 197765994