IL-2/IL-7-inducible factors pioneer the path to T cell differentiation in advance of lineage-defining factors

Sarah L Bevington, Peter Keane, Jake K Soley, Saskia Tauch, Dominika W Gajdasik, Remi Fiancette, Veronika Matei-Rascu, Claire M Willis, David R Withers, Peter N Cockerill

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
106 Downloads (Pure)

Abstract

When dormant naïve T cells first become activated by antigen-presenting cells, they express the autocrine growth factor IL-2 which transforms them into rapidly dividing effector T cells. During this process, hundreds of genes undergo epigenetic reprogramming for efficient activation, and also for potential reactivation after they return to quiescence as memory T cells. However, the relative contributions of IL-2 and T cell receptor signaling to this process are unknown. Here, we show that IL-2 signaling is required to maintain open chromatin at hundreds of gene regulatory elements, many of which control subsequent stimulus-dependent alternative pathways of T cell differentiation. We demonstrate that IL-2 activates binding of AP-1 and STAT5 at sites that can subsequently bind lineage-determining transcription factors, depending upon what other external factors exist in the local T cell environment. Once established, priming can also be maintained by the stroma-derived homeostatic cytokine IL-7, and priming diminishes if Il7r is subsequently deleted in vivo. Hence, IL-2 is not just a growth factor; it lays the foundation for T cell differentiation and immunological memory.

Original languageEnglish
Article numbere105220
JournalThe EMBO journal
Early online date15 Sep 2020
DOIs
Publication statusE-pub ahead of print - 15 Sep 2020

Bibliographical note

©2020 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords

  • IL-2
  • differentiation
  • memory T cell
  • priming
  • transcription factor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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