Genetic Causes of Human NK Cell Deficiency and Their Effect on NK Cell Subsets

Mace, Emily M.; Orange, Jordan S.

doi:10.3389/fimmu.2016.00545

Cited by 73 publications

(67 citation statements)

References 72 publications

(105 reference statements)

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“…These include mutations in the STAT and PI3K signaling pathways, as well as many cytoskeletal regulators. While full consideration of all of these is beyond the scope of this review, it is worthwhile to consider a few more recent advances beyond what has been already reviewed elsewhere to help understand what can be learned about NK cells from PIDs with NK cell features.…”

Section: Primary Immune Deficiencies With Nk Cell Featuresmentioning

confidence: 99%

“…While the majority of PIDs that are associated with an NK cell abnormality include both functional and phenotypic aberrations, a number of relevant developments have been reported since recent reviews on NK cells in PIDs have been published . Several of these are reviewed here in order to be able to contextualize the derivative biology in light of advances in the NK cell field.…”

Section: Primary Immune Deficiencies With Nk Cell Featuresmentioning

confidence: 99%

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Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

Mace

Orange

2018

Immunological Reviews

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129

107

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Human NK cells are innate immune effectors that play a critical roles in the control of viral infection and malignancy. The importance of their homeostasis and function can be demonstrated by the study of patients with primary immunodeficiencies (PID), which are part of the family of diseases known as inborn defects of immunity. While NK cells are affected in many PIDs in ways that may contribute to a patient’s clinical phenotype, a small number of PIDs have an NK cell abnormality as their major immunological defect. These PIDs can be collectively referred to as NK cell deficiency disorders (NKD), and include effects upon NK cell numbers, subsets and/or functions. The clinical impact of NKD can be severe including fatal viral infection, with particular susceptibility to herpesviral infections, such as cytomegalovirus, varicella zoster virus and Epstein-Barr virus. While NKD is rare, studies of these diseases are important for defining specific requirements for human NK cell development and homeostasis. New themes in NK cell biology are emerging through the study of both known and novel NKD, particularly those affecting cell cycle and DNA damage repair, as well as broader PIDs having substantive impact upon NK cells. In addition, the discovery of NKD that affect other innate lymphoid cell (ILC) subsets opens new doors for better understanding the relationship between conventional NK cells and other ILC subsets. Here we describe the biology underlying human NKD, particularly in the context of new insights into innate immune cell function, including a discussion of recently described NKD with accompanying effects on ILC subsets. Given the impact of these disorders upon human immunity with a common focus upon NK cells, the unifying message of a critical role for NK cells in human host defense singularly emerges.

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Section: Primary Immune Deficiencies With Nk Cell Featuresmentioning

confidence: 99%

Section: Primary Immune Deficiencies With Nk Cell Featuresmentioning

confidence: 99%

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

Mace

Orange

2018

Immunological Reviews

Self Cite

129

107

View full text Add to dashboard Cite

show abstract

“…In light of the functional and phenotypic overlap of T cells and NK cells, the specific requirement for adequate NK cell function in humans is highlighted by the identification and characterization of patients with selective NK cell deficiencies and who succumb to uncontrolled viral infections, particularly those belonging to the herpes family of viruses (Mace and Orange, 2016). Moreover, from the ground-breaking translational work of Velardi, Ravetch, Levy, and several other scientists, it is clear that human NK cell effector function has a critical role in the direct elimination of malignancy (Clynes et al, 2000; Ruggeri et al, 2002; Weng and Levy, 2003).…”

Section: Introductionmentioning

confidence: 99%

The Broad Spectrum of Human Natural Killer Cell Diversity

et al. 2017

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SUMMARY Natural killer (NK) cells provide protection against infectious pathogens and cancer. For decades it has been appreciated that two major NK cell subsets (CD56bright and CD56dim) exist in humans and have distinct anatomical localization patterns, phenotypes, and functions in immunity. In light of this traditional NK cell dichotomy, it is now clear that the spectrum of human NK cell diversity is much broader than originally appreciated as a result of variegated surface receptor, intracellular signaling molecule, and transcription factor expression; tissue-specific imprinting; and foreign antigen exposure. The recent discoveries of tissue-resident NK cell developmental intermediates, non-NK innate lymphoid cells, and the capacity for NK cells to adapt and differentiate into long-lived memory cells has added further complexity to this field. Here we review our current understanding of the breadth and generation of human NK cell diversity.

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“…According to specialized literature, NK cell deficiencies can be categorized in two major groups, named classical NK cell deficiency (CNKD) and functional NK cell deficiency (FNKD). In CNKD, patients have a marked and persistent reduction in the number of NK cells in peripheral blood, typically below 1%, whereas in FNKD, NK cells are normal or slightly decreased in numbers, but their function is impaired …”

Section: Nk Cell Recognition Of Human Cancer Cellsmentioning

confidence: 99%

“…Interestingly, one the earliest clinical manifestations is the susceptibility to HPV‐related diseases along with severe herpes virus infections. As consequence of all these viral infections, increased rates of malignancies are observed, including cervical cancer …”

Section: Nk Cell Recognition Of Human Cancer Cellsmentioning

confidence: 99%

From the “missing self” hypothesis to adaptive NK cells: Insights of NK cell-mediated effector functions in immune surveillance

Cruz-Muñoz

Valenzuela-Vázquez

Sánchez-Herrera

et al. 2019

Journal of Leukocyte Biology

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The original discovery of NK cells approximately 40 yr ago was based on their unique capability to kill tumor cells without prior sensitization or priming, a process named natural cytotoxicity. Since then, several studies have documented that NK cells can kill hematopoietic and nonhematopoietic cancer cells. NK cells also recognize and kill cells that have undergone viral infections. Besides natural cytotoxicity, NK cells are also major effectors of antibody‐dependent cell cytotoxicity (ADCC). Therefore, NK cells are well “armed” to recognize and mount immune responses against “insults” that result from cell transformation and viral infections. Because of these attributes, an essential role of NK cells in tumor surveillance was noted. Indeed, several studies have shown a correlation between impaired NK cell cytotoxicity and a higher risk of developing cancer. This evidence led to the idea that cancer initiation and progress is intimately related to an abnormal or misdirected immune response. Whereas all these ideas remain current, it is also true that NK cells represent a heterogeneous population with different abilities to secrete cytokines and to mediate cytotoxic functions. In addition, recent data has shown that NK cells are prone to suffer epigenetic modifications resulting in the acquisition of previously unrecognized attributes such as memory and long‐term survival. Such NK cells, referred as “adaptive” or “memory‐like,” also display effector functions that are not necessarily equal to those observed in conventional NK cells. Given the new evidence available, it is essential to discuss the conceptual reasoning and misconceptions regarding the role of NK cells in immune surveillance and immunotherapy.

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Genetic Causes of Human NK Cell Deficiency and Their Effect on NK Cell Subsets

Cited by 73 publications

References 72 publications

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

The Broad Spectrum of Human Natural Killer Cell Diversity

From the “missing self” hypothesis to adaptive NK cells: Insights of NK cell-mediated effector functions in immune surveillance

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