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  1. Article ; Online: Bearing a grudge-How human natural killer cells remember past insults.

    Mace, Emily M

    Science immunology

    2023  Volume 8, Issue 79, Page(s) eadg4688

    Abstract: Natural killer (NK) cell pathogen-specific memory is selected and maintained in the absence of antigen receptor rearrangement. ...

    Abstract Natural killer (NK) cell pathogen-specific memory is selected and maintained in the absence of antigen receptor rearrangement.
    MeSH term(s) Humans ; Killer Cells, Natural
    Language English
    Publishing date 2023-01-06
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.adg4688
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  2. Article ; Online: Profiling natural killers in COVID-19.

    Mace, Emily M

    The Journal of allergy and clinical immunology

    2022  Volume 149, Issue 4, Page(s) 1223–1224

    MeSH term(s) COVID-19 ; Humans ; Killer Cells, Natural ; SARS-CoV-2
    Language English
    Publishing date 2022-01-17
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2022.01.002
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  3. Article ; Online: Human natural killer cells: Form, function, and development.

    Mace, Emily M

    The Journal of allergy and clinical immunology

    2022  Volume 151, Issue 2, Page(s) 371–385

    Abstract: Human natural killer (NK) cells are innate lymphoid cells that mediate important effector functions in the control of viral infection and malignancy. Their ability to distinguish "self" from "nonself" and lyse virally infected and tumorigenic cells ... ...

    Abstract Human natural killer (NK) cells are innate lymphoid cells that mediate important effector functions in the control of viral infection and malignancy. Their ability to distinguish "self" from "nonself" and lyse virally infected and tumorigenic cells through germline-encoded receptors makes them important players in maintaining human health and a powerful tool for immunotherapeutic applications and fighting disease. This review introduces our current understanding of NK cell biology, including key facets of NK cell differentiation and the acquisition and execution of NK cell effector function. Further, it addresses the clinical relevance of NK cells in both primary immunodeficiency and immunotherapy. It is intended to provide an up-to-date and comprehensive overview of this important and interesting innate immune effector cell subset.
    MeSH term(s) Humans ; Immunity, Innate ; Killer Cells, Natural ; Immunotherapy ; Virus Diseases ; Neoplasms/therapy ; Neoplasms/pathology
    Language English
    Publishing date 2022-10-01
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2022.09.022
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  4. Article ; Online: A WICB 50th Favorite: Rapid lytic granule convergence to the MTOC in natural killer cells is dependent on dynein but not cytolytic commitment.

    Reed, Abigail E / Mace, Emily M

    Molecular biology of the cell

    2022  Volume 33, Issue 2, Page(s) fe2

    MeSH term(s) Cytoplasmic Granules/metabolism ; Dyneins/metabolism ; Killer Cells, Natural/metabolism ; Microtubule-Organizing Center/metabolism
    Chemical Substances Dyneins (EC 3.6.4.2)
    Language English
    Publishing date 2022-01-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E21-04-0218
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    Zs.A 2853: Show issues Location:
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    Zs.MO 410: Show issues

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  5. Article ; Online: CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover.

    Martinez, Amera L / Shannon, Michael J / Sloan, Tyler / Mace, Emily M

    Molecular biology of the cell

    2024  Volume 35, Issue 5, Page(s) ar64

    Abstract: Natural killer (NK) cells patrol tissue to mediate lysis of virally infected and tumorigenic cells. Human NK cells are typically identified by their expression of neural cell adhesion molecule (NCAM, CD56), yet despite its ubiquitous expression on NK ... ...

    Abstract Natural killer (NK) cells patrol tissue to mediate lysis of virally infected and tumorigenic cells. Human NK cells are typically identified by their expression of neural cell adhesion molecule (NCAM, CD56), yet despite its ubiquitous expression on NK cells, CD56 remains a poorly understood protein on immune cells. CD56 has been previously demonstrated to play roles in NK cell cytotoxic function and cell migration. Specifically, CD56-deficient NK cells have impaired cell migration on stromal cells and CD56 is localized to the uropod of NK cells migrating on stroma. Here, we show that CD56 is required for NK cell migration on ICAM-1 and is required for the establishment of persistent cell polarity and unidirectional actin flow. The intracellular domain of CD56 (NCAM-140) is required for its function and the loss of CD56 leads to enlarged actin foci and sequestration of phosphorylated Pyk2 accompanied by increased size and frequency of activated LFA-1 clusters. Together, these data identify a role for CD56 in regulating human NK cell migration through modulation of actin dynamics and integrin turnover.
    MeSH term(s) Humans ; Neural Cell Adhesion Molecules/metabolism ; Actins/metabolism ; CD56 Antigen/metabolism ; Killer Cells, Natural ; Lymphocyte Function-Associated Antigen-1/metabolism ; Cell Movement
    Chemical Substances Neural Cell Adhesion Molecules ; Actins ; CD56 Antigen ; Lymphocyte Function-Associated Antigen-1
    Language English
    Publishing date 2024-03-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E23-12-0463
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    Zs.MO 410: Show issues

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  6. Article ; Online: An inference model gives insights into innate immune adaptation and repertoire diversity.

    Qin, Yawei / Mace, Emily M / Barton, John P

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 38, Page(s) e2305859120

    Abstract: The innate immune system is the body's first line of defense against infection. Natural killer (NK) cells, a vital part of the innate immune system, help to control infection and eliminate cancer. Studies have identified a vast array of receptors that NK ...

    Abstract The innate immune system is the body's first line of defense against infection. Natural killer (NK) cells, a vital part of the innate immune system, help to control infection and eliminate cancer. Studies have identified a vast array of receptors that NK cells use to discriminate between healthy and unhealthy cells. However, at present, it is difficult to explain how NK cells will respond to novel stimuli in different environments. In addition, the expression of different receptors on individual NK cells is highly stochastic, but the reason for these variegated expression patterns is unclear. Here, we studied the recognition of unhealthy target cells as an inference problem, where NK cells must distinguish between healthy targets with normal variability in ligand expression and ones that are clear "outliers." Our mathematical model fits well with experimental data, including NK cells' adaptation to changing environments and responses to different target cells. Furthermore, we find that stochastic, "sparse" receptor expression profiles are best able to detect a variety of possible threats, in agreement with experimental studies of the NK cell repertoire. While our study was specifically motivated by NK cells, our model is general and could also apply more broadly to explain principles of target recognition for other immune cell types.
    MeSH term(s) Acclimatization ; Erythrocytes, Abnormal ; Gene Expression ; Immunity, Innate
    Language English
    Publishing date 2023-09-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2305859120
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    Zs.A 1148: Show issues Location:
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  7. Article: Phosphoinositide-3-Kinase Signaling in Human Natural Killer Cells: New Insights from Primary Immunodeficiency.

    Mace, Emily M

    Frontiers in immunology

    2018  Volume 9, Page(s) 445

    Abstract: Human natural killer (NK) cells play a critical role in the control of viral infections and malignancy. Their importance in human health and disease is illustrated by severe viral infections in patients with primary immunodeficiencies that affect NK cell ...

    Abstract Human natural killer (NK) cells play a critical role in the control of viral infections and malignancy. Their importance in human health and disease is illustrated by severe viral infections in patients with primary immunodeficiencies that affect NK cell function and/or development. The recent identification of patients with phosphoinositide-3-kinase (PI3K)-signaling pathway mutations that can cause primary immunodeficiency provides valuable insight into the role that PI3K signaling plays in human NK cell maturation and lytic function. There is a rich literature that demonstrates a requirement for PI3K in multiple key aspects of NK cell biology, including development/maturation, homing, priming, and function. Here, I briefly review these previous studies and place them in context with recent findings from the study of primary immunodeficiency patients, particularly those with hyperactivating mutations in PI3Kδ signaling.
    MeSH term(s) Cell Differentiation ; Cell Movement ; Cytotoxicity, Immunologic ; Enzyme Activation/genetics ; Humans ; Immunologic Deficiency Syndromes/genetics ; Immunologic Deficiency Syndromes/immunology ; Immunologic Deficiency Syndromes/metabolism ; Killer Cells, Natural/immunology ; Mutation/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction
    Chemical Substances Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Language English
    Publishing date 2018-03-07
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.00445
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  8. Article ; Online: Natural Killer Cell Integrins and Their Functions in Tissue Residency.

    Shannon, Michael J / Mace, Emily M

    Frontiers in immunology

    2021  Volume 12, Page(s) 647358

    Abstract: Integrins are transmembrane receptors associated with adhesion and migration and are often highly differentially expressed receptors amongst natural killer cell subsets in microenvironments. Tissue resident natural killer cells are frequently defined by ... ...

    Abstract Integrins are transmembrane receptors associated with adhesion and migration and are often highly differentially expressed receptors amongst natural killer cell subsets in microenvironments. Tissue resident natural killer cells are frequently defined by their differential integrin expression compared to other NK cell subsets, and integrins can further localize tissue resident NK cells to tissue microenvironments. As such, integrins play important roles in both the phenotypic and functional identity of NK cell subsets. Here we review the expression of integrin subtypes on NK cells and NK cell subsets with the goal of better understanding how integrin selection can dictate tissue residency and mediate function from the nanoscale to the tissue environment.
    MeSH term(s) Animals ; Cell Adhesion/immunology ; Cell Movement/immunology ; Chemokines/metabolism ; Extracellular Matrix/immunology ; Extracellular Matrix/metabolism ; Humans ; Integrins/chemistry ; Integrins/classification ; Integrins/metabolism ; Killer Cells, Natural/immunology ; Ligands ; Mice ; Protein Conformation ; Receptors, Chemokine/metabolism ; Signal Transduction/immunology
    Chemical Substances Chemokines ; Integrins ; Ligands ; Receptors, Chemokine
    Language English
    Publishing date 2021-03-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.647358
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  9. Article ; Online: Diversity of human NK cell developmental pathways defined by single-cell analyses.

    Seo, Seungmae / Mace, Emily M

    Current opinion in immunology

    2021  Volume 74, Page(s) 106–111

    Abstract: Human natural killer (NK) and innate lymphoid cells (ILCs) include diverse specialized phenotypic and functional subsets that reflect their roles as innate immune effector cells present in tissue and circulation. In recent years, significant advances ... ...

    Abstract Human natural killer (NK) and innate lymphoid cells (ILCs) include diverse specialized phenotypic and functional subsets that reflect their roles as innate immune effector cells present in tissue and circulation. In recent years, significant advances have been made in better defining their tissue resident phenotypes, developmental pathways, and phenotypic plasticity. Here we offer a brief review of new insights into human NK cell diversity specifically defined by next generation sequencing and single-cell transcriptomic studies and integrate these into our current models of human NK cell developmental trajectories and mature subsets. These studies highlight both a deeper understanding of innate lymphoid cell differentiation and homeostasis and underscore critical questions that remain outstanding in the field.
    MeSH term(s) Cell Differentiation ; Humans ; Immunity, Innate ; Killer Cells, Natural ; Phenotype ; Single-Cell Analysis
    Language English
    Publishing date 2021-11-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2021.11.001
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    Zs.MG 13: Show issues

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  10. Article ; Online: cellPLATO: an unsupervised method for identifying cell behaviour in heterogeneous cell trajectory data.

    Shannon, Michael J / Eisman, Shira E / Lowe, Alan R / Sloan, Tyler / Mace, Emily M

    Journal of cell science

    2024  

    Abstract: Advances in imaging, segmentation, and tracking have led to the routine generation of large and complex microscopy datasets. New tools are required to process this 'phenomics' type data. Cell PLasticity Analysis TOol (cellPLATO) is a Python-based ... ...

    Abstract Advances in imaging, segmentation, and tracking have led to the routine generation of large and complex microscopy datasets. New tools are required to process this 'phenomics' type data. Cell PLasticity Analysis TOol (cellPLATO) is a Python-based analysis software designed for measurement and classification of cell behaviours based on clustering features of cell morphology and motility. Used after segmentation and tracking, the tool extracts features from each cell per timepoint, using them to segregate cells into dimensionally reduced behavioural subtypes. Resultant cell tracks describe a 'behavioural ID' at each timepoint and similarity analysis allows the grouping of behavioural sequences into discrete trajectories with assigned IDs. Here, we use cellPLATO to investigate the role of IL-15 in modulating human NK cell migration on ICAM-1 or VCAM-1. We find 8 behavioural subsets of NK cells based on their shape and migration dynamics between single timepoints, and 4 trajectories based on sequences of these behaviours over time. Therefore, using cellPLATO we show that IL-15 increases plasticity between cell migration behaviours and that different integrin ligands induce different forms of NK cell migration.
    Language English
    Publishing date 2024-05-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.261887
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