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Identification of lineage-specifying cytokines that signal all CD8+-cytotoxic-lineage-fate 'decisions' in the thymus.

Ruth EtzenspergerTejas KadakiaXuguang TaiAmala AlagTerry I GuinterTakashi EbiharaBatu ErmanAlfred Singer
Published in: Nature immunology (2017)
T cell antigen receptor (TCR) signaling in the thymus initiates positive selection, but the CD8+-lineage fate is thought to be induced by cytokines after TCR signaling has ceased, although this remains controversial and unproven. We have identified four cytokines (IL-6, IFN-γ, TSLP and TGF-β) that did not signal via the common γ-chain (γc) receptor but that, like IL-7 and IL-15, induced expression of the lineage-specifying transcription factor Runx3d and signaled the generation of CD8+ T cells. Elimination of in vivo signaling by all six of these 'lineage-specifying cytokines' during positive selection eliminated Runx3d expression and completely abolished the generation of CD8+ single-positive thymocytes. Thus, this study proves that signaling during positive selection by lineage-specifying cytokines is responsible for all CD8+-lineage-fate 'decisions' in the thymus.
Keyphrases
  • single cell
  • transcription factor
  • poor prognosis
  • cell fate
  • dendritic cells
  • immune response
  • oxidative stress
  • long non coding rna
  • epithelial mesenchymal transition
  • transforming growth factor
  • anti inflammatory