T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate

Laura K. Mackay, Erica Wynne-Jones, David Freestone, Daniel G. Pellicci, Lisa A. Mielke, Dane M. Newman, Asolina Braun, Frederick Masson, Axel Kallies, Gabrielle T. Belz, Francis R. Carbone

Research output: Contribution to journalArticleResearchpeer-review

207 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1101-1111
Number of pages11
JournalImmunity
Volume43
Issue number6
DOIs
Publication statusPublished - 15 Dec 2015
Externally publishedYes

Keywords

  • Peripheral immunity
  • T-box transcription factors
  • TGF-β
  • Tissue-resident memory T cells

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