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Cardinal features of immune memory in innate lymphocytes

Nature Immunology volume 24, pages 1803–1812 (2023)Cite this article

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Abstract

The ability of vertebrates to ‘remember’ previous infections had once been attributed exclusively to adaptive immunity. We now appreciate that innate lymphocytes also possess memory properties akin to those of adaptive immune cells. In this Review, we draw parallels from T cell biology to explore the key features of immune memory in innate lymphocytes, including quantity, quality, and location. We discuss the signals that trigger clonal or clonal-like expansion in innate lymphocytes, and highlight recent studies that shed light on the complex cellular and molecular crosstalk between metabolism, epigenetics, and transcription responsible for differentiating innate lymphocyte responses towards a memory fate. Additionally, we explore emerging evidence that activated innate lymphocytes relocate and establish themselves in specific peripheral tissues during infection, which may facilitate an accelerated response program akin to those of tissue-resident memory T cells.

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Fig. 1: Advantage of numerical abundance.
Fig. 2: Triad of molecular adaptations.
Fig. 3: Convenience of tissue redistribution.

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Acknowledgements

The authors apologize to all those whose significant and valuable contributions could not be cited or discussed in this manuscript owing to space limitations. We thank members of the Sun lab for helpful feedback on the manuscript. J.C.S. was supported by the Ludwig Center for Cancer Immunotherapy, the American Cancer Society, the Burroughs Wellcome Fund, and the NIH (AI100874, AI130043, AI155558, and P30CA008748).

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Authors and Affiliations

  1. Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Endi K. Santosa & Joseph C. Sun

  2. Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY, USA

    Endi K. Santosa & Joseph C. Sun

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  1. Endi K. Santosa
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J.C.S. and E.K.S. contributed equally to all aspects of this article.

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Correspondence to Joseph C. Sun.

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Nature Immunology thanks Jeffrey Miller and the other, anonymous, reviewers for their contribution to the peer review of this work. Primary Handling Editor: Jamie D. K. Wilson, in collaboration with the Nature Immunology team.

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Santosa, E.K., Sun, J.C. Cardinal features of immune memory in innate lymphocytes. Nat Immunol 24, 1803–1812 (2023). https://doi.org/10.1038/s41590-023-01607-w

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