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Interactions between innate and adaptive lymphocytes

Abstract

Innate lymphocytes — including natural killer cells and the recently discovered innate lymphoid cells — have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. The contribution of the adaptive immune system to the coordination of innate lymphocyte responses is less well understood. In this Opinion article, we review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which T cells of the adaptive immune system function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential roles of regulatory and helper T cells in these processes, and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes.

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Figure 1: Innate and adaptive lymphocyte subsets.
Figure 2: Interactions of innate lymphocytes.
Figure 3: A model for IL-2-dependent adaptive–innate lymphocyte crosstalk.

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Acknowledgements

A.Y.R. is supported by a US National Institutes of Health grant (R37 AI034206) and by the Ludwig Center at Memorial Sloan-Kettering Cancer Center (MSKCC), New York, USA. A.Y.R. is an investigator at the Howard Hughes Medical Center, New York, USA. G.G. is an Irvington Fellow of the Cancer Research Institute at MSKCC. The authors would like to thank J. C. Sun and the members of the Rudensky and Sun laboratories for helpful discussions. The authors would like to apologize to those investigators whose related work they were unable to discuss or quote owing to space limitations.

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Glossary

Alarmins

Prefabricated molecules (for example, interleukin-33) that are released upon cell and tissue damage by epithelial, stromal and myeloid cells to activate the immune system. The potency of some alarmins is regulated locally — for example, by proteolytic cleavage.

Group 1 ILCs

(Group 1 innate lymphoid cells). This group of ILCs includes natural killer cells and ILC1s.

ILC1

(Type 1 innate lymphoid cell). A subset of 'innate helper' cells that is characterized by expression of the transcription factor T-bet and the ability to produce interferon-γ in response to interleukin-12. ILC1s may have crucial functions during infection with intracellular pathogens.

ILC2

(Type 2 innate lymphoid cell). A subset of 'innate helper' cells that is characterized by expression of the transcription factor GATA-binding protein 3 and the ability to produce interleukin-5 (IL-5) and IL-13 in response to IL-25 and IL-33. ILC2s have important roles during asthma and parasitic infection, as well as tissue homeostasis and fibrosis through the secretion of amphiregulin, for example.

ILC3s

(Type 3 innate lymphoid cells). These 'innate helper' cells are characterized by expression of the transcription factor retinoic acid receptor-related orphan receptor-γt and the ability to produce interleukin-17 (IL-17) and IL-22 in response to IL-23. ILC3s have crucial functions during bacterial infection, particularly in the intestine. ILC3s may also present antigens and contribute to immune tolerance against microbial symbionts.

Innate lymphoid cells

(ILCs). Recently discovered subsets of innate lymphocytes that seed peripheral organs, and produce 'helper' cytokines and tissue-protective factors that are crucial for barrier immunity.

Lymphoid tissue inducer cell

(LTi cell). A subset of group 3 ILCs that are characterized by expression of the transcription factor retinoic acid receptor-related orphan receptor-γt and the production of lymphotoxin α1β1. LTi cells are required for the development of secondary lymphoid organs, and may have functions that are important during chronic inflammation and for T cell memory.

Natural killer cells

(NK cells). Innate lymphocytes that can recognize and kill infected or cancerous cells. NK cells also produce interferon-γ and may have immunoregulatory functions.

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Gasteiger, G., Rudensky, A. Interactions between innate and adaptive lymphocytes. Nat Rev Immunol 14, 631–639 (2014). https://doi.org/10.1038/nri3726

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