T-box Transcription Factors Combine with the Cytokines TGF-beta and IL-15 to Control Tissue-Resident Memory T Cell Fate Academic Article uri icon

abstract

  • Tissue-resident memory T (Trm) cells contribute to local immune protection in non-lymphoid tissues such as skin and mucosa, but little is known about their transcriptional regulation. Here we showed that CD8(+)CD103(+) Trm cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. We demonstrated that the T-box transcription factors (TFs) Eomes and T-bet combined to control CD8(+)CD103(+) Trm cell formation, such that their coordinate downregulation was crucial for TGF-β cytokine signaling. TGF-β signaling, in turn, resulted in reciprocal T-box TF downregulation. However, whereas extinguishment of Eomes was necessary for CD8(+)CD103(+) Trm cell development, residual T-bet expression maintained cell surface interleukin-15 (IL-15) receptor β-chain (CD122) expression and thus IL-15 responsiveness. These findings indicate that the T-box TFs control the two cytokines, TGF-β and IL-15, which are pivotal for CD8(+)CD103(+) Trm cell development and survival.

authors

  • Mackay, LK
  • Wynne-Jones, E
  • Freestone, D
  • Pellicci, DG
  • Mielke, LA
  • Newman, DM
  • Braun, A
  • Masson, F
  • Kallies, A
  • Belz, GT
  • Carbone, FR

publication date

  • 2015