Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15

Lin, Syh‐Jae; Kuo, Ming‐Ling; Hsiao, Hsiu-Shan; Lee, Pei-Tzu; Lee, Wen-I; Chen, Ji-Yih; Huang, Jing‐Long

doi:10.1155/2019/4236562

Cited by 20 publications

(12 citation statements)

References 33 publications

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“…We found that iNKT cells in SLE patients were deficient in number and showed poor response to α-GalCer stimulation, in agreement with previous studies [ 23 , 26 ]. We and others have previous shown the ability of IL-15 to regulate the phenotype and function of NK and NK T-like -cells in SLE patients [ 15 , 27 , 28 ]. Although IL-15 alone did not increase iNKT cell percentage in MNCs, it expanded the absolute counts of iNKT cells, and thus increased cell recovery.…”

Section: Discussionmentioning

confidence: 99%

Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15

et al. 2021

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CD1d-restricted invariant natural killer T cells (iNKT cells) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-15 is a pro-inflammatory cytokine which is over-expressed in SLE patients. In the present study, we investigated the iNKT cell expansion of mononuclear cells (MNCs) from SLE patients following 10 days’ culture with α-galactosylceramide (α-Galcer) and /or IL-15. We sought to determine the phenotypic and functional characteristics of the expanded iNKT cells compared to healthy controls and correlated with disease activity. We observed that 1. The percentages of Vα24+/Vβ11+ iNKT cells following 10-day incubation was lower in SLE groups compared to controls; 2. The percentages and absolute numbers of Vα24+/Vβ11+ iNKT cells were expanded by α-galactosylceramide (α-Galcer), and further enhanced with IL-15 in SLE patient, but the effect of IL-15 was much lower than controls; 3.IL-15 +α-Galcer expanded CD3+/CD56+ NKT-like cells from SLE patients, especially with active disease 4. The CD161+ Vα24+/Vβ11+ iNKT cells in SLE were more responsive to α-Galcer stimulation than the CD161- counterpart; 5. IL-15 decreased apoptosis of α-Galcer activated SLE iNKT cells; 6. IL-15 enhanced CD69, CD1d and CD11a expression on α-Galcer treated iNKT cells; 7. The IL-4 production of iNKT cells was decreased in SLE patients compared to controls; 8. IL-15 increased IFN-γ and IL-4 production of SLE iNKT cells; 8. IL-15 failed to augment the ability of iNKT cells to aid NK-mediated K562 cytolysis in SLE patients; 9. CD161 positivity, granzyme B and perforin expression of α-Galcer+IL-15 expanded iNKT cells correlated with C3 levels in SLE patients. Taken together, our results demonstrated numeric and functional deficiency of iNKT cells and their response to IL-15 in SLE patients. Our finding may provide insight for using adoptive iNKT cell therapy in autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15

et al. 2021

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“…Also, it was shown in the same study that the status of decreased CD56 dim NK cells was activated and their IFN- γ levels were increased. Granzyme B + CD56 bright cell ratios were found to be higher in active phase compared to in inactive phase of SLE and those in healthy individuals ( 252 ). In addition, TNF-α levels of CD56 dim NK cells but not CD56 bright NK cells from active SLE patients were demonstrated to be lower than inactive SLE patients and healthy individuals.…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 99%

The Role of Natural Killer Cells in Autoimmune Diseases

et al. 2021

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Natural killer (NK) cells, the large granular lymphocytes differentiated from the common lymphoid progenitors, were discovered in early 1970’s. They are members of innate immunity and were initially defined by their strong cytotoxicity against virus-infected cells and by their important effector functions in anti-tumoral immune responses. Nowadays, NK cells are classified among the recently discovered innate lymphoid cell subsets and have capacity to influence both innate and adaptive immune responses. Therefore, they can be considered as innate immune cells that stands between the innate and adaptive arms of immunity. NK cells don’t express T or B cell receptors and are recognized by absence of CD3. There are two major subgroups of NK cells according to their differential expression of CD16 and CD56. While CD16+CD56dim subset is best-known by their cytotoxic functions, CD16-CD56bright NK cell subset produces a bunch of cytokines comparable to CD4+ T helper cell subsets. Another subset of NK cells with production of interleukin (IL)-10 was named as NK regulatory cells, which has suppressive properties and could take part in immune-regulatory responses. Activation of NK cells is determined by a delicate balance of cell-surface receptors that have either activating or inhibitory properties. On the other hand, a variety of cytokines including IL-2, IL-12, IL-15, and IL-18 influence NK cell activity. NK-derived cytokines and their cytotoxic functions through induction of apoptosis take part in regulation of the immune responses and could contribute to the pathogenesis of many immune mediated diseases including ankylosing spondylitis, Behçet’s disease, multiple sclerosis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus and type-1 diabetes. Dysregulation of NK cells in autoimmune disorders may occur through multiple mechanisms. Thanks to the rapid developments in biotechnology, progressive research in immunology enables better characterization of cells and their delicate roles in the complex network of immunity. As NK cells stand in between innate and adaptive arms of immunity and “bridge” them, their contribution in inflammation and immune regulation deserves intense investigations. Better understanding of NK-cell biology and their contribution in both exacerbation and regulation of inflammatory disorders is a requisite for possible utilization of these multi-faceted cells in novel therapeutic interventions.

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“…A recent study showed that CD56 bright NK cells may contribute to SLE development. Serum IL-15 level was elevated in SLE patients, particularly those with active disease (55,56); and an increased number of peripheral blood Ki67 + CD56 bright NK cells was strongly correlated with elevated serum IL-15, clinical severity, and active nephritis in SLE patients (57). The high serum IL-15 level in SLE may be attributable to type I IFN-mediated DC activation; moreover, IL-15 induces the expression of Ki67 in NK cells, which stimulates NK cell proliferation and contributes to pathogenesis of SLE.…”

Section: Nk Cells and Autoimmune Diseases Nk Cells And Systemic Autoimentioning

confidence: 99%

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

2021

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Autoimmune diseases generally result from the loss of self-tolerance (i.e., failure of the immune system to distinguish self from non-self), and are characterized by autoantibody production and hyperactivation of T cells, which leads to damage of specific or multiple organs. Thus, autoimmune diseases can be classified as organ-specific or systemic. Genetic and environmental factors contribute to the development of autoimmunity. Recent studies have demonstrated the contribution of innate immunity to the onset of autoimmune diseases. Natural killer (NK) cells, which are key components of the innate immune system, have been implicated in the development of multiple autoimmune diseases such as systemic lupus erythematosus, type I diabetes mellitus, and autoimmune liver disease. However, NK cells have both protective and pathogenic roles in autoimmunity depending on the NK cell subset, microenvironment, and disease type or stage. In this work, we review the current knowledge of the varied roles of NK cell subsets in systemic and organic-specific autoimmune diseases and their clinical potential as therapeutic targets.

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Cytotoxic Function and Cytokine Production of Natural Killer Cells and Natural Killer T-Like Cells in Systemic Lupus Erythematosis Regulation with Interleukin-15

Cited by 20 publications

References 33 publications

Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15

Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15

The Role of Natural Killer Cells in Autoimmune Diseases

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

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