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

Etzensperger R., Kadakia T., Tai X., Alag A., Guinter T. I., Egawa T., ...Daha Fazla

NATURE IMMUNOLOGY, cilt.18, sa.11, ss.1218-1227, 2017 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 18 Sayı: 11
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1038/ni.3847
  • Dergi Adı: NATURE IMMUNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1218-1227
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

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-gamma, TSLP and TGF-beta) that did not signal via the common gamma-chain (gamma(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.