Genetic distinction between functional tissue-resident and conventional natural killer cells

Hu, Luni; Han, Mengwei; Deng, Yichen; Gong, Jianping; Hou, Zhonggang; Zeng, Yanyu; Zhang, Yime; He, Jiaqing; Zhong, Chao

doi:10.1016/j.isci.2023.107187

Cited by 3 publications

(4 citation statements)

References 60 publications

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“…Insights from uterus transplant studies support the peripheral origin of uterine NK cells, as NK cells in endometrial biopsies after transplantation are recipient-derived 32 . Additional studies identified that CD56 dim CD16+ cells have the potential to acquire a dNK phenotype under the influence of TGFβ 33–36 , gene expression profiles indicate that tissue resident NK cells are more likely derived from the less differentiated pbNK population, such as CD56 bright CD16-cells 11,19,37–39 .…”

Section: Introductionmentioning

confidence: 97%

“…For instance, CD8+ tissue-resident memory T cells (Trm) are characterized by distinct surface phenotypes and functionalities 5–8 , with studies revealing early tissue-adapted precursors and unique molecular signatures of residency 9 . Likewise, NK cells, which hold similarity to CD8+ T cells 10 , have been identified across various tissues and exhibit functional diversity beyond their circulatory counterparts 11 .…”

Section: Introductionmentioning

confidence: 99%

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Sequential Transcriptional Programs of Tissue Residency Drive Human Uterine NK Cell Development

Greene,

Asiimwe,

Wright

et al. 2024

Preprint

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The idea of tissue resident immune populations is a concept extending to the innate lymphocyte population of NK cells. One such population of tissue resident NK cell is decidual natural killer cells, which are critical for pregnancy success but the origin and development of these cells in the human uterus remain unclear. Here we use various single-cell approaches to identify the transcriptional programs governing uterine NK cell development in humans. These analyses suggest a developmental continuum from immature CD56bright precursors in the blood through a putative endometrial founder NK cell to mature tissue resident NK cells. Our work identifies a role for sequential programs of tissue residency in the differentiation of these cells, as differentiating trNK cells acquire early and late transcriptional programs of residency which coincide with acquisition of unique non-cytotoxic effector programs. Notably, we identified early residency programs in human endometrial trNK by expression of NR4A2, AP-1 transcription factors, and other immediate early response genes that were shared with CD8 tissue resident memory T cells in mice, suggesting conservation of transcriptional programs of early tissue residency programs across species and cell types. Late residency programs were guided by TGFβ, which promoted expression of various integrins and trNK subset diversification within the non-pregnant endometrium. Altogether, these data identify the molecular foundations for endometrial trNK heterogeneity and suggest that the uterine NK diversity observed during pregnancy is established before embryo implantation and intimately tied to residency programming.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Sequential Transcriptional Programs of Tissue Residency Drive Human Uterine NK Cell Development

Greene,

Asiimwe,

Wright

et al. 2024

Preprint

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“…The bone marrow is the primary site of natural killer cell development and may also develop and mature in stimulated lymphoid organs, including the tonsils, spleen, and lymph nodes [ 22 ]. Subsequently, based on their tissue-resident properties, natural killer cells can be classified into classical natural killer cells with cycling properties and tissue-resident natural killer cells [ 23 ].…”

Section: Origin Of Natural Killer Cell and Cancer Immunotherapymentioning

confidence: 99%

Natural killer cell-derived exosome-based cancer therapy: from biological roles to clinical significance and implications

Si,

Gao,

2024

Mol Cancer

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Natural killer (NK) cells are important immune cells in the organism and are the third major type of lymphocytes besides T cells and B cells, which play an important function in cancer therapy. In addition to retaining the tumor cell killing function of natural killer cells, natural killer cell-derived exosomes cells also have the characteristics of high safety, wide source, easy to preserve and transport. At the same time, natural killer cell-derived exosomes are easy to modify, and the engineered exosomes can be used in combination with a variety of current cancer therapies, which not only enhances the therapeutic efficacy, but also significantly reduces the side effects. Therefore, this review summarizes the source, isolation and modification strategies of natural killer cell-derived exosomes and the combined application of natural killer cell-derived engineered exosomes with other antitumor therapies, which is expected to accelerate the clinical translation process of natural killer cell-derived engineered exosomes in cancer therapy.

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“…Ex vivo expansion using IL-12/15/18 priming to generate long lived memory NK cells is a promising area of research with clinical benefit obtained in early phase studies (1,7,8). IL-21 is a pleiotropic cytokine that is involved in activation of NK and CD8 T cells and is specifically associated with tissue resident NK cells(9). IL-21 has been shown to induce excellent expansion of NK cells ex-vivo using feeder cell lines expressing membrane bound IL-21, which appears to mitigate the senescence associated with other cytokine regimens (10).…”

Section: Introductionmentioning

confidence: 99%

Impact of IL-21 on Natural Killer cell proliferation and function – a mathematical and functional assessment

Biondo,

Nayak,

Möker

et al. 2024

Preprint

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Natural killer (NK) cells are currently in use as immunotherapeutic agents for cancer. Many different cytokines are used to generate NK cells including IL-2, IL-12, IL-15 and IL-18 in solution and membrane bound IL-21. These cytokines drive NK cell activation through the integration of STAT and NF-κB pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations. We integrated functional assays for NK cells cultured in a variety of cytokine combinations with feature selection and mechanistic regression models. Our regression model successfully predicts NK cell proliferation for different cytokine combinations and indicates synergy between STAT3 and NF-κB transcription factors. Use of IL-21 in solution in the priming, but not post-priming phase of NK cell culture resulted in optimal NK cell proliferation, without compromising cytotoxicity or IFN-γ secretion against hepatocellular carcinoma cell lines. Our work provides a mathematical framework for interrogating NK cell activation for cancer immunotherapy.

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Genetic distinction between functional tissue-resident and conventional natural killer cells

Cited by 3 publications

References 60 publications

Sequential Transcriptional Programs of Tissue Residency Drive Human Uterine NK Cell Development

Sequential Transcriptional Programs of Tissue Residency Drive Human Uterine NK Cell Development

Natural killer cell-derived exosome-based cancer therapy: from biological roles to clinical significance and implications

Impact of IL-21 on Natural Killer cell proliferation and function – a mathematical and functional assessment

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