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  1. Book ; Online: Molecular and Cellular Pathways in NK Cell Development

    Sitnicka, Ewa / Bryceson, Yenan / Freud, Aharon / Mace, Emily

    2020  

    Keywords Medicine ; Immunology ; NK cells ; developmental and maturation stages ; regulatory pathways ; disease-induced defects ; clinical applications
    Size 1 electronic resource (177 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021231308
    ISBN 9782889639779 ; 2889639770
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Book ; Online: Molecular mechanisms regulating cytotoxic lymphocyte development and function, and their associations to human diseases

    Bryceson, Yenan / Krzewski, Konrad

    2015  

    Abstract: Cytotoxic lymphocytes, comprised of NK cells and cytotoxic T cells, play a pivotal role in immune defense. By directed release of perforin-containing lytic granules, NK and cytotoxic T cells can eradicate pathogen-infected, tumorigenic, and otherwise ... ...

    Abstract Cytotoxic lymphocytes, comprised of NK cells and cytotoxic T cells, play a pivotal role in immune defense. By directed release of perforin-containing lytic granules, NK and cytotoxic T cells can eradicate pathogen-infected, tumorigenic, and otherwise stressed cells. By the virtue of cytokine and chemokine secretion, they can influence other cells of the immune system. Through these processes, cytotoxic lymphocytes also contribute to the maintenance of immune homeostasis. In recent years, much progress has been made with respect to the mechanisms by which cytotoxic lymphocytes develop, differentiate, and exert their effector functions. In a clinical perspective, a wide variety of mutations impairing cytotoxic lymphocyte development and/or function have been associated with immunodeficiency and severe diseases in humans. Aberrant activity of cytotoxic T cells and/or NK cells has been linked to an increased susceptibility to viral infections, persistent inflammation, cancer and autoimmunity. In addition, lymphocyte cytotoxic activity may be harnessed therapeutically to target tumor cells in different adoptive cellular therapy regimes, or through the use of recombinant antibodies. Still, a number of questions remain in regards to how cytotoxic lymphocytes develop, their relationships and plasticity, as well as the mechanisms dictating target cell discrimination, lytic granule release and induction of target cell death. In this Research Topic we encourage submission of research articles, reviews, perspectives, or methods on cytotoxic lymphocyte development and function, their relation to the pathogenesis or treatment of different diseases, as well as comparison between similarities and/or differences in their effector functions. Considering the clinical significance of NK cells and cytotoxic T cells, we aim to provide a range of articles summarizing the current knowledge on the identification and elucidation of the mechanisms governing cytotoxic lymphocyte activity
    Keywords Immunologic diseases. Allergy ; Medicine (General)
    Size 1 electronic resource (163 p.)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT020090202
    ISBN 9782889192793 ; 2889192792
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  3. Article ; Online: Rough operators: sphingomyelinase inhibitors spike NK cells to kill cancer.

    Carlsten, Mattias / Bryceson, Yenan T

    Signal transduction and targeted therapy

    2023  Volume 8, Issue 1, Page(s) 316

    MeSH term(s) Humans ; Sphingomyelin Phosphodiesterase/genetics ; Killer Cells, Natural ; Neoplasms/drug therapy ; Neoplasms/genetics
    Chemical Substances Sphingomyelin Phosphodiesterase (EC 3.1.4.12)
    Language English
    Publishing date 2023-08-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2886872-9
    ISSN 2059-3635 ; 2095-9907
    ISSN (online) 2059-3635
    ISSN 2095-9907
    DOI 10.1038/s41392-023-01550-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Neuroinflammation Associated With Inborn Errors of Immunity.

    Lindahl, Hannes / Bryceson, Yenan T

    Frontiers in immunology

    2022  Volume 12, Page(s) 827815

    Abstract: The advent of high-throughput sequencing has facilitated genotype-phenotype correlations in congenital diseases. This has provided molecular diagnosis and benefited patient management but has also revealed substantial phenotypic heterogeneity. Although ... ...

    Abstract The advent of high-throughput sequencing has facilitated genotype-phenotype correlations in congenital diseases. This has provided molecular diagnosis and benefited patient management but has also revealed substantial phenotypic heterogeneity. Although distinct neuroinflammatory diseases are scarce among the several thousands of established congenital diseases, elements of neuroinflammation are increasingly recognized in a substantial proportion of inborn errors of immunity, where it may even dominate the clinical picture at initial presentation. Although each disease entity is rare, they collectively can constitute a significant proportion of neuropediatric patients in tertiary care and may occasionally also explain adult neurology patients. We focus this review on the signs and symptoms of neuroinflammation that have been reported in association with established pathogenic variants in immune genes and suggest the following subdivision based on proposed underlying mechanisms: autoinflammatory disorders, tolerance defects, and immunodeficiency disorders. The large group of autoinflammatory disorders is further subdivided into IL-1β-mediated disorders, NF-κB dysregulation, type I interferonopathies, and hemophagocytic syndromes. We delineate emerging pathogenic themes underlying neuroinflammation in monogenic diseases and describe the breadth of the clinical spectrum to support decisions to screen for a genetic diagnosis and encourage further research on a neglected phenomenon.
    MeSH term(s) Alleles ; Animals ; Autoimmunity ; Biomarkers ; Cytokines/metabolism ; Genetic Association Studies ; Genetic Diseases, Inborn/complications ; Genetic Diseases, Inborn/diagnosis ; Genetic Diseases, Inborn/genetics ; Genetic Predisposition to Disease ; Humans ; Immune Tolerance ; Immunity/genetics ; Inflammation Mediators/metabolism ; Magnetic Resonance Imaging ; Mutation ; Neuroinflammatory Diseases/diagnosis ; Neuroinflammatory Diseases/etiology ; Phenotype
    Chemical Substances Biomarkers ; Cytokines ; Inflammation Mediators
    Language English
    Publishing date 2022-01-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.827815
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Genetics and pathophysiology of haemophagocytic lymphohistiocytosis.

    Meeths, Marie / Bryceson, Yenan T

    Acta paediatrica (Oslo, Norway : 1992)

    2021  Volume 110, Issue 11, Page(s) 2903–2911

    Abstract: Haemophagocytic lymphohistiocytosis (HLH) represents a life-threatening hyperinflammatory syndrome. Familial studies have established autosomal and X-linked recessive causes of HLH, highlighting a pivotal role for lymphocyte cytotoxicity in the control ... ...

    Abstract Haemophagocytic lymphohistiocytosis (HLH) represents a life-threatening hyperinflammatory syndrome. Familial studies have established autosomal and X-linked recessive causes of HLH, highlighting a pivotal role for lymphocyte cytotoxicity in the control of certain virus infections and immunoregulation. Recently, a more complex etiological framework has emerged, linking HLH predisposition to variants in genes required for metabolism or immunity to intracellular pathogens. We review genetic predisposition to HLH and discuss how molecular insights have provided fundamental knowledge of the immune system as well as detailed pathophysiological understanding of hyperinflammatory diseases, highlighting new treatment strategies.
    MeSH term(s) Genetic Predisposition to Disease ; Humans ; Lymphohistiocytosis, Hemophagocytic/genetics ; Virus Diseases
    Language English
    Publishing date 2021-07-12
    Publishing country Norway
    Document type Journal Article ; Review
    ZDB-ID 203487-6
    ISSN 1651-2227 ; 0365-1436 ; 0803-5253
    ISSN (online) 1651-2227
    ISSN 0365-1436 ; 0803-5253
    DOI 10.1111/apa.16013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: IL2RB

    Campbell, Tessa M / Bryceson, Yenan T

    The Journal of experimental medicine

    2019  Volume 216, Issue 6, Page(s) 1231–1233

    Abstract: How the IL-2 receptor β-chain specifically shapes immunity has remained enigmatic. In this issue ... ...

    Abstract How the IL-2 receptor β-chain specifically shapes immunity has remained enigmatic. In this issue of
    MeSH term(s) Humans ; Killer Cells, Natural ; Mutation
    Language English
    Publishing date 2019-05-08
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20190546
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  7. Article ; Online: HLH: genomics illuminates pathophysiological diversity.

    Tesi, Bianca / Bryceson, Yenan T

    Blood

    2018  Volume 132, Issue 1, Page(s) 5–7

    MeSH term(s) Child ; Genomics ; Humans ; Lymphohistiocytosis, Hemophagocytic
    Language English
    Publishing date 2018-07-05
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2018-05-845818
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Natural killer cells in inflammation and autoimmunity.

    Zitti, Beatrice / Bryceson, Yenan T

    Cytokine & growth factor reviews

    2018  Volume 42, Page(s) 37–46

    Abstract: First described 40 years ago, natural killer (NK) cells represent the founding members of the innate lymphoid cell (ILC) family. They were initially defined by their ability to kill cancer cells of hematopoietic origin. More recently, NK cells are ... ...

    Abstract First described 40 years ago, natural killer (NK) cells represent the founding members of the innate lymphoid cell (ILC) family. They were initially defined by their ability to kill cancer cells of hematopoietic origin. More recently, NK cells are recognized not only for their ability to kill infected or malignant cells, but also for mediating cytotoxicity against a range of normal immune cells. They thereby play an important physiological role in controlling immune responses and maintaining homeostasis. Besides cytotoxic activity, NK cells activation is accompanied by secretion of pro-inflammatory cytokines. Hence, NK cells have the potential to act both in driving inflammation and in restricting adaptive immune responses that may otherwise lead to excessive inflammation or even autoimmunity. Here, we highlight how NK cell activity is linked to inflammasome activation and review new molecular insights to the roles of NK cells in inflammation and autoimmunity. Furthermore, in light of new insights to NK cell differentiation and memory, we deliberate on how distinct NK cell subsets may impact immunoregulatory functions. Hypothetically, memory-like or adaptive NK cells could drive NK cell-mediated autoreactive diseases. Together, new findings underscore the complex yet important physiological roles of NK cells in both promoting inflammation and exerting immunoregulation and maintenance of immune homeostasis. Insights raise intriguing questions as to how NK cells themselves maintain self-tolerance.
    MeSH term(s) Adaptive Immunity/immunology ; Animals ; Autoimmune Diseases/immunology ; Autoimmunity/immunology ; Cytokines/immunology ; Humans ; Immunity, Innate/immunology ; Inflammation/immunology ; Killer Cells, Natural/immunology
    Chemical Substances Cytokines
    Language English
    Publishing date 2018-08-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1330534-7
    ISSN 1879-0305 ; 1359-6101
    ISSN (online) 1879-0305
    ISSN 1359-6101
    DOI 10.1016/j.cytogfr.2018.08.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Natural killer cell biology illuminated by primary immunodeficiency syndromes in humans.

    Voss, Matthias / Bryceson, Yenan T

    Clinical immunology (Orlando, Fla.)

    2017  Volume 177, Page(s) 29–42

    Abstract: Natural killer (NK) cells are innate immune cytotoxic effector cells well known for their role in antiviral immunity and tumor immunosurveillance. In parts, this knowledge stems from rare inherited immunodeficiency disorders in humans that abrogate NK ... ...

    Abstract Natural killer (NK) cells are innate immune cytotoxic effector cells well known for their role in antiviral immunity and tumor immunosurveillance. In parts, this knowledge stems from rare inherited immunodeficiency disorders in humans that abrogate NK cell function leading to immune impairments, most notably associated with a high susceptibility to viral infections. Phenotypically, these disorders range from deficiencies selectively affecting NK cells to complex general immune defects that affect NK cells but also other immune cell subsets. Moreover, deficiencies may be associated with reduced NK cell numbers or rather impair specific NK cell effector functions. In recent years, genetic defects underlying the various NK cell deficiencies have been uncovered and have triggered investigative efforts to decipher the molecular mechanisms underlying these disorders. Here we review the associations between inherited human diseases and NK cell development as well as function, with a particular focus on defects in NK cell exocytosis and cytotoxicity. Furthermore we outline how reports of diverse genetic defects have shaped our understanding of NK cell biology.
    MeSH term(s) Animals ; Genetic Variation ; Humans ; Immunologic Deficiency Syndromes/genetics ; Immunologic Deficiency Syndromes/immunology ; Killer Cells, Natural/immunology
    Language English
    Publishing date 2017-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2015.11.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Viral host range factors antagonize pathogenic SAMD9 and SAMD9L variants.

    Gahr, Stine / Perinetti Casoni, Giovanna / Falk-Paulsen, Maren / Maschkowitz, Gregor / Bryceson, Yenan T / Voss, Matthias

    Experimental cell research

    2023  Volume 425, Issue 2, Page(s) 113541

    Abstract: SAMD9 and SAMD9L encode homologous interferon-induced genes that can inhibit cellular translation as well as proliferation and can restrict viral replication. Gain-of-function (GoF) variants in these ancient, yet rapidly evolving genes are associated ... ...

    Abstract SAMD9 and SAMD9L encode homologous interferon-induced genes that can inhibit cellular translation as well as proliferation and can restrict viral replication. Gain-of-function (GoF) variants in these ancient, yet rapidly evolving genes are associated with life-threatening disease in humans. Potentially driving population sequence diversity, several viruses have evolved host range factors that antagonize cell-intrinsic SAMD9/SAMD9L function. Here, to gain insights into the molecular regulation of SAMD9/SAMD9L activity and to explore the prospect of directly counteracting the activity of pathogenic variants, we examined whether dysregulated activity of pathogenic SAMD9/SAMD9L variants can be modulated by the poxviral host range factors M062, C7 and K1 in a co-expression system. We established that the virally encoded proteins retain interactions with select SAMD9/SAMD9L missense GoF variants. Furthermore, expression of M062, C7 and K1 could principally ameliorate the translation-inhibiting and growth-restrictive effect instigated by ectopically expressed SAMD9/SAMD9L GoF variants, yet with differences in potency. K1 displayed the greatest potency and almost completely restored cellular proliferation and translation in cells co-expressing SAMD9/SAMD9L GoF variants. However, neither of the viral proteins tested could antagonize a truncated SAMD9L variant associated with severe autoinflammation. Our study demonstrates that pathogenic SAMD9/SAMD9L missense variants can principally be targeted through molecular interactions, opening an opportunity for therapeutic modulation of their activity. Moreover, it provides novel insights into the complex intramolecular regulation of SAMD9/SAMD9L activity.
    MeSH term(s) Humans ; Host Specificity ; Tumor Suppressor Proteins/genetics ; Viral Proteins/genetics ; Transcription Factors ; Virus Replication/genetics ; Intracellular Signaling Peptides and Proteins/genetics
    Chemical Substances Tumor Suppressor Proteins ; Viral Proteins ; Transcription Factors ; SAMD9 protein, human ; Intracellular Signaling Peptides and Proteins
    Language English
    Publishing date 2023-03-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1493-x
    ISSN 1090-2422 ; 0014-4827
    ISSN (online) 1090-2422
    ISSN 0014-4827
    DOI 10.1016/j.yexcr.2023.113541
    Database MEDical Literature Analysis and Retrieval System OnLINE

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