Title | Epigenetic control of innate and adaptive immune memory. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Lau CM, Adams NM, Geary CD, Weizman O-E, Rapp M, Pritykin Y, Leslie CS, Sun JC |
Journal | Nat Immunol |
Volume | 19 |
Issue | 9 |
Pagination | 963-972 |
Date Published | 2018 09 |
ISSN | 1529-2916 |
Keywords | Adaptive Immunity, Animals, CD8-Positive T-Lymphocytes, Cells, Cultured, Chromatin, Clonal Selection, Antigen-Mediated, Epigenesis, Genetic, Gene Expression Profiling, Herpesviridae Infections, Immunity, Innate, Immunologic Memory, Killer Cells, Natural, Mice, Mice, Inbred C57BL, Mice, Knockout, Muromegalovirus, STAT1 Transcription Factor, STAT4 Transcription Factor |
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. |
DOI | 10.1038/s41590-018-0176-1 |
Alternate Journal | Nat. Immunol. |
PubMed ID | 30082830 |
PubMed Central ID | PMC6225771 |
Grant List | R01 AI100874 / AI / NIAID NIH HHS / United States T32 CA009149 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States F30 AI136239 / AI / NIAID NIH HHS / United States R01 AI130043 / AI / NIAID NIH HHS / United States |
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