Epigenetic control of innate and adaptive immune memory

Nat Immunol. 2018 Sep;19(9):963-972. doi: 10.1038/s41590-018-0176-1. Epub 2018 Aug 6.

Abstract

Clonal expansion and immunological memory are hallmark features of the mammalian adaptive immune response and essential for prolonged host control of pathogens. Recent work demonstrates that natural killer (NK) cells of the innate immune system also exhibit these adaptive traits during infection. Here we demonstrate that differentiating and 'memory' NK cells possess distinct chromatin accessibility states and that their epigenetic profiles reveal a 'poised' regulatory program at the memory stage. Furthermore, we elucidate how individual STAT transcription factors differentially control epigenetic and transcriptional states early during infection. Finally, concurrent chromatin profiling of the canonical CD8+ T cell response against the same infection demonstrated parallel and distinct epigenetic signatures defining NK cells and CD8+ T cells. Overall, our study reveals the dynamic nature of epigenetic modifications during the generation of innate and adaptive lymphocyte memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Clonal Selection, Antigen-Mediated
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Herpesviridae Infections / immunology*
  • Immunity, Innate
  • Immunologic Memory
  • Killer Cells, Natural / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muromegalovirus / physiology*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • STAT4 Transcription Factor / genetics
  • STAT4 Transcription Factor / metabolism*

Substances

  • Chromatin
  • STAT1 Transcription Factor
  • STAT4 Transcription Factor