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

Ruth Etzensperger, Tejas Kadakia, Xuguang Tai, Amala Alag, Terry I. Guinter, Takeshi Egawa, Batu Erman, Alfred Singer

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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-3, TSLP and TGF-β) that did not signal via the common 3-chain (3 c) 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.

Original languageEnglish
Pages (from-to)1218-1227
Number of pages10
JournalNature immunology
Volume18
Issue number11
DOIs
StatePublished - Oct 18 2017

Fingerprint Dive into the research topics of 'Identification of lineage-specifying cytokines that signal all CD8 + -cytotoxic-lineage-fate 'decisions' in the thymus'. Together they form a unique fingerprint.

  • Cite this

    Etzensperger, R., Kadakia, T., Tai, X., Alag, A., Guinter, T. I., Egawa, T., Erman, B., & Singer, A. (2017). Identification of lineage-specifying cytokines that signal all CD8 + -cytotoxic-lineage-fate 'decisions' in the thymus. Nature immunology, 18(11), 1218-1227. https://doi.org/10.1038/ni.3847