Infection induces tissue-resident memory NK cells that safeguard tissue health

Iona S. Schuster; Xavier Y.X. Sng; Colleen M. Lau; David R. Powell; Orr El Weizman; Peter Fleming; Georgia E.G. Neate; Valentina Voigt; Sam Sheppard; Andreas I. Maraskovsky; Sheridan Daly; Motoko Koyama; Geoffrey R. Hill; Stephen J. Turner; Timothy E. O'Sullivan; Joseph C. Sun; Christopher E. Andoniou; Mariapia A. Degli-Esposti

doi:10.1016/j.immuni.2023.01.016

Infection induces tissue-resident memory NK cells that safeguard tissue health

Iona S. Schuster, Xavier Y.X. Sng, Colleen M. Lau, David R. Powell, Orr El Weizman, Peter Fleming, Georgia E.G. Neate, Valentina Voigt, Sam Sheppard, Andreas I. Maraskovsky, Sheridan Daly, Motoko Koyama, Geoffrey R. Hill, Stephen J. Turner, Timothy E. O'Sullivan, Joseph C. Sun, Christopher E. Andoniou, Mariapia A. Degli-Esposti

Research output: Contribution to journal › Article › Research › peer-review

21 Citations (Scopus)

Abstract

Tissue health is dictated by the capacity to respond to perturbations and then return to homeostasis. Mechanisms that initiate, maintain, and regulate immune responses in tissues are therefore essential. Adaptive immunity plays a key role in these responses, with memory and tissue residency being cardinal features. A corresponding role for innate cells is unknown. Here, we have identified a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells were recruited in a CX3CR1-dependent manner to the salivary glands where they formed NKRM cells, a long-lived, tissue-resident population that prevented autoimmunity via TRAIL-dependent elimination of CD4⁺ T cells. Thus, NK cells develop adaptive-like features, including long-term residency in non-lymphoid tissues, to modulate inflammation, restore immune equilibrium, and preserve tissue health. Modulating the functions of NKRM cells may provide additional strategies to treat inflammatory and autoimmune diseases.

Original language	English
Pages (from-to)	531-546.e6
Number of pages	22
Journal	Immunity
Volume	56
Issue number	3
DOIs	https://doi.org/10.1016/j.immuni.2023.01.016
Publication status	Published - 14 Mar 2023

Keywords

autoimmunity
CD4 T cells
cytomegalovirus
immune regulation
inflammation
memory
natural killer cells
Sjogren's syndrome
tissue residency
viral infection

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2023.01.016

Cite this

Schuster, I. S., Sng, X. Y. X., Lau, C. M., Powell, D. R., Weizman, O. E., Fleming, P., Neate, G. E. G., Voigt, V., Sheppard, S., Maraskovsky, A. I., Daly, S., Koyama, M., Hill, G. R., Turner, S. J., O'Sullivan, T. E., Sun, J. C., Andoniou, C. E., & Degli-Esposti, M. A. (2023). Infection induces tissue-resident memory NK cells that safeguard tissue health. Immunity, 56(3), 531-546.e6. https://doi.org/10.1016/j.immuni.2023.01.016

@article{24127ff23d6a49499ff18036e0d2d3d1,

title = "Infection induces tissue-resident memory NK cells that safeguard tissue health",

abstract = "Tissue health is dictated by the capacity to respond to perturbations and then return to homeostasis. Mechanisms that initiate, maintain, and regulate immune responses in tissues are therefore essential. Adaptive immunity plays a key role in these responses, with memory and tissue residency being cardinal features. A corresponding role for innate cells is unknown. Here, we have identified a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells were recruited in a CX3CR1-dependent manner to the salivary glands where they formed NKRM cells, a long-lived, tissue-resident population that prevented autoimmunity via TRAIL-dependent elimination of CD4+ T cells. Thus, NK cells develop adaptive-like features, including long-term residency in non-lymphoid tissues, to modulate inflammation, restore immune equilibrium, and preserve tissue health. Modulating the functions of NKRM cells may provide additional strategies to treat inflammatory and autoimmune diseases.",

keywords = "autoimmunity, CD4 T cells, cytomegalovirus, immune regulation, inflammation, memory, natural killer cells, Sjogren's syndrome, tissue residency, viral infection",

author = "Schuster, {Iona S.} and Sng, {Xavier Y.X.} and Lau, {Colleen M.} and Powell, {David R.} and Weizman, {Orr El} and Peter Fleming and Neate, {Georgia E.G.} and Valentina Voigt and Sam Sheppard and Maraskovsky, {Andreas I.} and Sheridan Daly and Motoko Koyama and Hill, {Geoffrey R.} and Turner, {Stephen J.} and O'Sullivan, {Timothy E.} and Sun, {Joseph C.} and Andoniou, {Christopher E.} and Degli-Esposti, {Mariapia A.}",

note = "Funding Information: We thank Nicole La Gruta and Jamie Rossjohn for insightful discussions and critical reading of the manuscript and Ian Rankin for assistance with graphical design. We thank Simone Ross and the Bioresources Animal Research Staff (Perth, Western Australia) and the following Monash University platforms for technical support: FlowCore, Monash Animal Research Platform, Monash Bioinformatics Platform, Micromon, Monash Histology Platform, and Monash Micro Imaging. We acknowledge the use of the Integrated Genomics Operation Core, funded by the NCI Cancer Center Support Grant (CCSG, P30CA08748), Cycle for Survival, and the Marie-Jos{\'e}e and Henry R. Kravis Center for Molecular Oncology. This work was supported by National Health and Medical Research Council of Australia (NHMRC) grants (1125357; 2004397) (M.A.D.-E. and C.E.A.) and an NHMRC Principal Research Fellowship (1119298) (M.A.D.-E.); Raine Medical Research Foundation Healy Research Collaboration Award (I.S.S.); National Institutes of Health grants (AI100874, AI130043), the Ludwig Center for Cancer Immunotherapy, the American Cancer Society, and the Burroughs Wellcome Fund (J.C.S.); and Cancer Research Institute, Carson Family Fellowship (C.M.L.). Conceptualization, M.A.D.-E. I.S.S. and C.E.A.; resources and reagents, M.A.D.-E. J.C.S. and G.R.H.; investigation, I.S.S. X.Y.X.S. C.E.A. C.M.L. D.R.P. O.-E.W. P.F. G.E.G.N. V.V. S.S. A.I.M. S.D. M.K. and T.E.O'S.; data analysis, I.S.S. X.Y.X.S. C.E.A. C.M.L. D.R.P. S.J.T. T.E.O. J.C.S. and M.A.D.-E.; funding acquisition, M.A.D.-E. and J.C.S.; manuscript writing, I.S.S. M.A.D.-E. and C.E.A. with contributions from all the other authors. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We thank Nicole La Gruta and Jamie Rossjohn for insightful discussions and critical reading of the manuscript and Ian Rankin for assistance with graphical design. We thank Simone Ross and the Bioresources Animal Research Staff (Perth, Western Australia) and the following Monash University platforms for technical support: FlowCore, Monash Animal Research Platform, Monash Bioinformatics Platform, Micromon, Monash Histology Platform, and Monash Micro Imaging. We acknowledge the use of the Integrated Genomics Operation Core, funded by the NCI Cancer Center Support Grant (CCSG, P30CA08748 ), Cycle for Survival , and the Marie-Jos{\'e}e and Henry R. Kravis Center for Molecular Oncology . This work was supported by National Health and Medical Research Council of Australia (NHMRC) grants ( 1125357 ; 2004397 ) (M.A.D.-E. and C.E.A.) and an NHMRC Principal Research Fellowship ( 1119298 ) (M.A.D.-E.); Raine Medical Research Foundation Healy Research Collaboration Award (I.S.S.); National Institutes of Health grants ( AI100874 , AI130043 ), the Ludwig Center for Cancer Immunotherapy , the American Cancer Society , and the Burroughs Wellcome Fund (J.C.S.); and Cancer Research Institute , Carson Family Fellowship (C.M.L.). Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = mar,

day = "14",

doi = "10.1016/j.immuni.2023.01.016",

language = "English",

volume = "56",

pages = "531--546.e6",

journal = "Immunity",

issn = "1074-7613",

publisher = "Elsevier",

number = "3",

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Schuster, IS , Sng, XYX, Lau, CM, Powell, DR, Weizman, OE, Fleming, P, Neate, GEG, Voigt, V, Sheppard, S, Maraskovsky, AI, Daly, S, Koyama, M, Hill, GR, Turner, SJ, O'Sullivan, TE, Sun, JC, Andoniou, CE & Degli-Esposti, MA 2023, 'Infection induces tissue-resident memory NK cells that safeguard tissue health', Immunity, vol. 56, no. 3, pp. 531-546.e6. https://doi.org/10.1016/j.immuni.2023.01.016

TY - JOUR

T1 - Infection induces tissue-resident memory NK cells that safeguard tissue health

AU - Schuster, Iona S.

AU - Sng, Xavier Y.X.

AU - Lau, Colleen M.

AU - Powell, David R.

AU - Weizman, Orr El

AU - Fleming, Peter

AU - Neate, Georgia E.G.

AU - Voigt, Valentina

AU - Sheppard, Sam

AU - Maraskovsky, Andreas I.

AU - Daly, Sheridan

AU - Koyama, Motoko

AU - Hill, Geoffrey R.

AU - Turner, Stephen J.

AU - O'Sullivan, Timothy E.

AU - Sun, Joseph C.

AU - Andoniou, Christopher E.

AU - Degli-Esposti, Mariapia A.

N1 - Funding Information: We thank Nicole La Gruta and Jamie Rossjohn for insightful discussions and critical reading of the manuscript and Ian Rankin for assistance with graphical design. We thank Simone Ross and the Bioresources Animal Research Staff (Perth, Western Australia) and the following Monash University platforms for technical support: FlowCore, Monash Animal Research Platform, Monash Bioinformatics Platform, Micromon, Monash Histology Platform, and Monash Micro Imaging. We acknowledge the use of the Integrated Genomics Operation Core, funded by the NCI Cancer Center Support Grant (CCSG, P30CA08748), Cycle for Survival, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology. This work was supported by National Health and Medical Research Council of Australia (NHMRC) grants (1125357; 2004397) (M.A.D.-E. and C.E.A.) and an NHMRC Principal Research Fellowship (1119298) (M.A.D.-E.); Raine Medical Research Foundation Healy Research Collaboration Award (I.S.S.); National Institutes of Health grants (AI100874, AI130043), the Ludwig Center for Cancer Immunotherapy, the American Cancer Society, and the Burroughs Wellcome Fund (J.C.S.); and Cancer Research Institute, Carson Family Fellowship (C.M.L.). Conceptualization, M.A.D.-E. I.S.S. and C.E.A.; resources and reagents, M.A.D.-E. J.C.S. and G.R.H.; investigation, I.S.S. X.Y.X.S. C.E.A. C.M.L. D.R.P. O.-E.W. P.F. G.E.G.N. V.V. S.S. A.I.M. S.D. M.K. and T.E.O'S.; data analysis, I.S.S. X.Y.X.S. C.E.A. C.M.L. D.R.P. S.J.T. T.E.O. J.C.S. and M.A.D.-E.; funding acquisition, M.A.D.-E. and J.C.S.; manuscript writing, I.S.S. M.A.D.-E. and C.E.A. with contributions from all the other authors. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We thank Nicole La Gruta and Jamie Rossjohn for insightful discussions and critical reading of the manuscript and Ian Rankin for assistance with graphical design. We thank Simone Ross and the Bioresources Animal Research Staff (Perth, Western Australia) and the following Monash University platforms for technical support: FlowCore, Monash Animal Research Platform, Monash Bioinformatics Platform, Micromon, Monash Histology Platform, and Monash Micro Imaging. We acknowledge the use of the Integrated Genomics Operation Core, funded by the NCI Cancer Center Support Grant (CCSG, P30CA08748 ), Cycle for Survival , and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology . This work was supported by National Health and Medical Research Council of Australia (NHMRC) grants ( 1125357 ; 2004397 ) (M.A.D.-E. and C.E.A.) and an NHMRC Principal Research Fellowship ( 1119298 ) (M.A.D.-E.); Raine Medical Research Foundation Healy Research Collaboration Award (I.S.S.); National Institutes of Health grants ( AI100874 , AI130043 ), the Ludwig Center for Cancer Immunotherapy , the American Cancer Society , and the Burroughs Wellcome Fund (J.C.S.); and Cancer Research Institute , Carson Family Fellowship (C.M.L.). Publisher Copyright: © 2023 Elsevier Inc.

PY - 2023/3/14

Y1 - 2023/3/14

N2 - Tissue health is dictated by the capacity to respond to perturbations and then return to homeostasis. Mechanisms that initiate, maintain, and regulate immune responses in tissues are therefore essential. Adaptive immunity plays a key role in these responses, with memory and tissue residency being cardinal features. A corresponding role for innate cells is unknown. Here, we have identified a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells were recruited in a CX3CR1-dependent manner to the salivary glands where they formed NKRM cells, a long-lived, tissue-resident population that prevented autoimmunity via TRAIL-dependent elimination of CD4+ T cells. Thus, NK cells develop adaptive-like features, including long-term residency in non-lymphoid tissues, to modulate inflammation, restore immune equilibrium, and preserve tissue health. Modulating the functions of NKRM cells may provide additional strategies to treat inflammatory and autoimmune diseases.

AB - Tissue health is dictated by the capacity to respond to perturbations and then return to homeostasis. Mechanisms that initiate, maintain, and regulate immune responses in tissues are therefore essential. Adaptive immunity plays a key role in these responses, with memory and tissue residency being cardinal features. A corresponding role for innate cells is unknown. Here, we have identified a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells were recruited in a CX3CR1-dependent manner to the salivary glands where they formed NKRM cells, a long-lived, tissue-resident population that prevented autoimmunity via TRAIL-dependent elimination of CD4+ T cells. Thus, NK cells develop adaptive-like features, including long-term residency in non-lymphoid tissues, to modulate inflammation, restore immune equilibrium, and preserve tissue health. Modulating the functions of NKRM cells may provide additional strategies to treat inflammatory and autoimmune diseases.

KW - autoimmunity

KW - CD4 T cells

KW - cytomegalovirus

KW - immune regulation

KW - inflammation

KW - memory

KW - natural killer cells

KW - Sjogren's syndrome

KW - tissue residency

KW - viral infection

UR - http://www.scopus.com/inward/record.url?scp=85149601075&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2023.01.016

DO - 10.1016/j.immuni.2023.01.016

M3 - Article

C2 - 36773607

AN - SCOPUS:85149601075

SN - 1074-7613

VL - 56

SP - 531-546.e6

JO - Immunity

JF - Immunity

IS - 3

ER -

Infection induces tissue-resident memory NK cells that safeguard tissue health

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Erratum: Infection induces tissue-resident memory NK cells that safeguard tissue health (Immunity (2023) 56(3) (531–546.e6), (S1074761323000262), (10.1016/j.immuni.2023.01.016))

Developing improved therapies for cytomegalovirus infections by overcoming viral strain-diversity.

Immunoregulation and immunity to viral infection

Effective therapies to treat viral infections and their complications in transplantation

Animal Research Platform (MARP)

Bioinformatics Platform

FlowCore

Cite this

Infection induces tissue-resident memory NK cells that safeguard tissue health

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Research output

Erratum: Infection induces tissue-resident memory NK cells that safeguard tissue health (Immunity (2023) 56(3) (531–546.e6), (S1074761323000262), (10.1016/j.immuni.2023.01.016))

Projects

Developing improved therapies for cytomegalovirus infections by overcoming viral strain-diversity.

Immunoregulation and immunity to viral infection

Effective therapies to treat viral infections and their complications in transplantation

Equipment

Animal Research Platform (MARP)

Bioinformatics Platform

FlowCore

Cite this