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Inscribing the core memories of killers

Cellular & Molecular Immunology volume 16, pages 104–105 (2019)Cite this article

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Recent studies on natural killer (NK) cells have challenged the dogma that immunological memory is a phenomenon restricted to the adaptive immune system. Specific interactions between the NK cell receptor Ly49H and the murine cytomegalovirus virus (MCMV)-encoded glycoprotein m157 result in selective expansion of the Ly49H + NK cell subpopulation and the establishment of a long-lived memory-like population.1,2,3 Further, memory NK cells show augmented IFNγ responses, and transfer of the memory population into naive mice confers enhanced protection against infection-induced mortality.1 These observations along with cytotoxicity and cytokine secretion functions that overlap with CD8 T cells have led to the description of NK cells as a bridge between the innate and adaptive immune systems.4 Despite their common features, important distinctions exist between the specificity, kinetics, activation, and efficacy of NK and CD8 T cell responses. Furthermore, while the chromatin landscape of naive, effector, and memory CD8 T cells is increasingly well defined,5 less is known about changes in gene accessibility that occur as NK cells gain memory properties. A recent report by Lau et al. uncovers key epigenetic changes that are associated with the formation of memory NK cells and lays the foundation for the identification of a core epigenetic signature shared by memory NK and T cells.6

Interestingly, during this initial period the chromatin is most dramatically changing at putative enhancer elements within introns and intergenic regions rather than at promotor sequences. This suggests that, unlike CD8 T cells which acquire progressive gain of access in promotors,5 NK cells rely more on changes in enhancer accessibility to drive gene expression as the cells evolve from naive to effector and memory states. In fact, naive NK cells show much higher levels of gene accessibility than naive T cells, and the ATAC-seq analysis clusters naive NK cells closer to memory T cells rather than naive or effector T cells. Thus, naive NK cells may be more predisposed to respond, possibly reflecting their key innate surveillance roles. Similarly, helper-like innate lymphoid cells do not undergo large-scale chromatin remodeling once they are developmentally mature, even upon stimulation, whereas their adaptive counterpart, CD4 T cells, require activation to initiate remodeling at effector gene loci.7

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References

  1. Sun, J. C., Beilke, J. N. & Lanier, L. L. Adaptive immune features of natural killer cells. Nature 457, 557–561 (2009).

    Article  CAS  Google Scholar 

  2. Arase, H., Mocarski, E. S., Campbell, A. E., Hill, A. B. & Lanier, L. L. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296, 1323–1326 (2002).

    Article  CAS  Google Scholar 

  3. Sun, J. C., Beilke, J. N. & Lanier, L. L. Immune memory redefined: characterizing the longevity of natural killer cells. Immunol. Rev. 236, 83–94 (2010).

    Article  CAS  Google Scholar 

  4. Vivier, E. et al. Innate or adaptive immunity? The example of natural killer cells. Science 331, 44–49 (2011).

    Article  CAS  Google Scholar 

  5. Henning, A. N., Roychoudhuri, R. & Restifo, N. P. Epigenetic control of CD8( + ) T cell differentiation. Nat. Rev. Immunol. 18, 340–356 (2018).

    Article  CAS  Google Scholar 

  6. Lau, C. M. et al. Epigenetic control of innate and adaptive immune memory. Nat. Immunol. 19, 963–972 (2018).

    Article  CAS  Google Scholar 

  7. Shih, H. Y. et al. Developmental acquisition of regulomes underlies innate lymphoid cell functionality. Cell 165, 1120–1133 (2016).

    Article  CAS  Google Scholar 

  8. Saeed, S. et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345, 1251086 (2014).

    Article  Google Scholar 

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Acknowledgements

We wish to thank Ashlyn Anderson, Shannon Kahan, and Boyoung Shin for critical discussions and helpful comments.

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  1. Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, 35294, United States

    Sarah J. Dulson & Laurie E. Harrington

  2. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, United States

    Allan J. Zajac

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  1. Sarah J. Dulson
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  2. Laurie E. Harrington
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Correspondence to Allan J. Zajac.

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Dulson, S.J., Harrington, L.E. & Zajac, A.J. Inscribing the core memories of killers. Cell Mol Immunol 16, 104–105 (2019). https://doi.org/10.1038/s41423-018-0178-9

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