Journal
NATURE IMMUNOLOGY
Volume 19, Issue 9, Pages 963-+Publisher
NATURE RESEARCH
DOI: 10.1038/s41590-018-0176-1
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Funding
- Cycle for Survival
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology
- NIH [CA009149, U01 HG007893, AI100874, AI130043, P30CA008748]
- National Institute of General Medical Sciences of the NIH [T32GM007739]
- NIH National Institute of Allergy and Infectious Diseases [F30 AI136239]
- German Academic Exchange Service (DAAD
- Germany)
- Ludwig Center for Cancer Immunotherapy
- Burroughs Wellcome Fund
- American Cancer Society
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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.
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