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

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

doi:10.1016/j.immuni.2023.01.016

Cited by 25 publications

(54 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Albeit not significant, we observed a mild expansion of the CD4 + T cell compartment in NK cell depleted naïve animals. This somewhat corroborates the NK-mediated regulation of CD4 + T cells observed by Schuster and colleagues, although the CD4 + T cell expansion appears to be more pronounced in infected animals 37 .…”

Section: Discussionsupporting

confidence: 90%

“…Besides effector functions, recent evidence suggests a regulatory role for NK cells, at least during viral infections. For instance, Schuster and colleagues recently identified a population of tissue-resident memory-like NK cells, which prevent autoimmunity via TRAIL-dependent elimination of CD4 + T cells during chronic viral infection 36,37 . Albeit not significant, we observed a mild expansion of the CD4 + T cell compartment in NK cell depleted naïve animals.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

PD-1 Mediated Regulation of Unique Activated CD8⁺T Cells by NK Cells in the Submandibular Gland

Borys,

Reilly,

Magill

et al. 2023

Preprint

View full text Add to dashboard Cite

The increasing utilization of anti-PD-1 immune checkpoint blockade (ICB) has led to the emergence of immune-related adverse events (irAEs), including sicca syndrome. Interestingly, we found that the submandibular gland (SMG) of PD-1 deficient mice harbors a large population of CD8+ T cells, reminiscing ICB induced sicca. This phenotype was also observed in the SMG of both NK cell-depleted C57BL/6 animals and NK cell-deficient animals. Mechanistically, using mice conditionally deficient for PD-L1 in the NK cell lineage, we discovered that NK cells regulate CD8+ T cell homeostasis via the PD-1/PD-L1 axis in this organ. Importantly, single-cell RNA sequencing of PD-1 deficient SMG CD8+ T cells reveals a unique transcriptional profile consistent with TCR activation. These cells have limited TCR diversity and phenotypically overlap with GzmK+ CD8+ T autoimmune cells identified in primary Sjogren syndrome patients. These insights into NK cell immunoregulation in the SMG, and the consequences of disrupted CD8+ T cell homeostasis, provide opportunities for preventing the development of irAEs.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

PD-1 Mediated Regulation of Unique Activated CD8⁺T Cells by NK Cells in the Submandibular Gland

Borys,

Reilly,

Magill

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Interestingly, TRAIL has previously been involved in the molecular mechanism allowing elimination of HIV-1 infected CD4+ T cells by NK cells ex vivo and controlling the reservoir size in humanized mice ( 90–92 ) and increased expression of this molecule had been reported in IL-15 expanded NK cells from PWH ( 93 ). Also, TRAIL has been proposed as a mechanism of killing utilized by tissue-resident NK cells in salivary glands in autoimmune Sjogreńs syndrome ( 94 ) and autoimmune diabetes ( 95 ). However, the role of TRAIL had not been previously investigated in NKG2C+ memory NK cells or in the context of immunotherapy against HIV-1.…”

Section: Discussionmentioning

confidence: 99%

Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

Sánchez-Cerrillo,

Popova,

Agudo-Lera

et al. 2024

Preprint

View full text Add to dashboard Cite

Natural Killer (NK) cells are promising tools for the development of immunotherapies targeting persistently infected CD4+ T cells to potentially achieve remission in people with HIV-1 (PWH). However, the chronicity of HIV-1 infection limits the functional properties of NK cells, and additional approaches are needed to potentiate their cytotoxic activity against HIV-1-infected cells. In the present study, we analyzed the reinvigoration of functional NK cells from PWH after priming with autologous dendritic cells (DC) stimulated with nanoparticles containing Poly I:C (Nano-PIC). We show that improved natural cytotoxic function in NK cell from PWH associates with increased proportions of NKG2C+CD57- precursors of memory NK, which eliminate HIV-1 infected CD4+ T cells mainly through the TRAIL receptor. In addition, expression of TIGIT but not TIM3 limited increase in NKG2C+ memory NK cell precursors and associated with persistent dysfunctionality of NK cells after stimulation with Nano PIC-DC. Blockade of TIGIT restored functional capacities of NK cell from PWH eliminating HIV-1 infected cellsin vitro. Moreover, combining of NK cell and Nano-PIC-DC with anti-TIGIT mAbs immunotherapy limited the expansion of HIV-1 infected cells in humanized immunodeficient NSG mice transplanted with CD4+ T cells from PWHin vivo. Such viral control was associated with preserved NKG2C memory NK cell precursors, increased expression of granzyme B and TRAIL on NK in tissue from transplanted NSG mice. Together, combination of Nano-PIC DC and anti-TIGIT antibodies may be a promising strategy to increase the efficacy of immunotherapies aimed at HIV-1 cure.One sentence summaryStimulation of memory NK with a combination of DC and anti-TIGIT antibodies increase their ability to eliminate HIV-1 infected CD4+ T cellsin vitroandin vivo.

show abstract

“…113,114,[118][119][120] Current evidence from mouse studies in the salivary gland and uterus supports the hypothesis that trNK cells are derived from circulating NK cells and are likely epigenetically imprinted based on tissue-specific factors. 121 Because the developmental and phenotypic differences between group 1 ILCs have been reviewed previously, 117 we will focus our discussion on studies detailing the impact of epigenetic modifications on the survival of distinct subsets of group 1 ILCs.…”

Section: Trafficking and Tissue-residencymentioning

confidence: 99%

No time to die: Epigenetic regulation of natural killer cell survival

Hermans,

O'Sullivan

2024

Immunological Reviews

View full text Add to dashboard Cite

SummaryNK cells are short‐lived innate lymphocytes that can mediate antigen‐independent responses to infection and cancer. However, studies from the past two decades have shown that NK cells can acquire transcriptional and epigenetic modifications during inflammation that result in increased survival and lifespan. These findings blur the lines between the innate and adaptive arms of the immune system, and suggest that the homeostatic mechanisms that govern the persistence of innate immune cells are malleable. Indeed, recent studies have shown that NK cells undergo continuous and strictly regulated adaptations controlling their survival during development, tissue residency, and following inflammation. In this review, we summarize our current understanding of the critical factors regulating NK cell survival throughout their lifespan, with a specific emphasis on the epigenetic modifications that regulate the survival of NK cells in various contexts. A precise understanding of the molecular mechanisms that govern NK cell survival will be important to enhance therapies for cancer and infectious diseases.

show abstract

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

Cited by 25 publications

References 68 publications

PD-1 Mediated Regulation of Unique Activated CD8⁺T Cells by NK Cells in the Submandibular Gland

PD-1 Mediated Regulation of Unique Activated CD8⁺T Cells by NK Cells in the Submandibular Gland

Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

No time to die: Epigenetic regulation of natural killer cell survival

Contact Info

Product

Resources

About

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

Cited by 25 publications

References 68 publications

PD-1 Mediated Regulation of Unique Activated CD8+T Cells by NK Cells in the Submandibular Gland

PD-1 Mediated Regulation of Unique Activated CD8+T Cells by NK Cells in the Submandibular Gland

Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

No time to die: Epigenetic regulation of natural killer cell survival

Contact Info

Product

Resources

About

PD-1 Mediated Regulation of Unique Activated CD8⁺T Cells by NK Cells in the Submandibular Gland

PD-1 Mediated Regulation of Unique Activated CD8⁺T Cells by NK Cells in the Submandibular Gland