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Inflammatory gene expression profile and defective interferon-γ and granzyme K in natural killer cells from systemic juvenile idiopathic arthritis patients

(2017) ARTHRITIS & RHEUMATOLOGY. 69(1). p.213-224
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Abstract
Objective: Systemic juvenile idiopathic arthritis (JIA) is an immunoinflammatory disease characterized by arthritis and systemic manifestations. The role of natural killer (NK) cells in the pathogenesis of systemic JIA remains unclear. The purpose of this study was to perform a comprehensive analysis of NK cell phenotype and functionality in patients with systemic JIA. Methods: Transcriptional alterations specific to NK cells were investigated by RNA sequencing of highly purified NK cells from 6 patients with active systemic JIA and 6 age-matched healthy controls. Cytokines (NK cell-stimulating and others) were quantified in plasma samples (n=18). NK cell phenotype and cytotoxic activity against tumor cells were determined (n=10), together with their interferon-gamma (IFN gamma)-producing function (n=8). Results: NK cells from the systemic JIA patients showed an altered gene expression profile compared to cells from the healthy controls, with enrichment of immunoinflammatory pathways, increased expression of innate genes including TLR4 and S100A9, and decreased expression of immune-regulating genes such as IL10RA and GZMK. In the patients' plasma, interleukin-18 (IL-18) levels were increased, and a decreased ratio of IFN gamma to IL-18 was observed. NK cells from the patients exhibited specific alterations in the balance of inhibitory and activating receptors, with decreased killer cell lectin-like receptor G1 and increased NKp44 expression. Although NK cells from the patients showed increased granzyme B expression, consistent with intact cytotoxicity and degranulation against a tumor cell line, decreased granzyme K expression in CD56(bright) NK cells and defective IL-18-induced IFN gamma production and signaling were demonstrated. Conclusion: NK cells are active players in the inflammatory environment typical of systemic JIA. Although their cytotoxic function is globally intact, subtle defects in NK-related pathways, such as granzyme K expression and IL-18-driven IFN gamma production, may contribute to the immunoinflammatory dysregulation in this disease.
Keywords
MACROPHAGE ACTIVATION SYNDROME, HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, RHEUMATOID-ARTHRITIS, MULTIPLE-SCLEROSIS, PERIPHERAL-BLOOD, IL-1 BLOCKADE, PATHOGENESIS, DYSFUNCTION, INTERLEUKIN-18, CYTOKINES

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MLA
Put, Karen, et al. “Inflammatory Gene Expression Profile and Defective Interferon-γ and Granzyme K in Natural Killer Cells from Systemic Juvenile Idiopathic Arthritis Patients.” ARTHRITIS & RHEUMATOLOGY, vol. 69, no. 1, 2017, pp. 213–24, doi:10.1002/art.39933.
APA
Put, K., Vandenhaute, J., Avau, A., van Nieuwenhuijze, A., Brisse, E., Dierckx, T., … Matthys, P. (2017). Inflammatory gene expression profile and defective interferon-γ and granzyme K in natural killer cells from systemic juvenile idiopathic arthritis patients. ARTHRITIS & RHEUMATOLOGY, 69(1), 213–224. https://doi.org/10.1002/art.39933
Chicago author-date
Put, Karen, Jessica Vandenhaute, Anneleen Avau, Annemarie van Nieuwenhuijze, Ellen Brisse, Tim Dierckx, Omer Rutgeerts, et al. 2017. “Inflammatory Gene Expression Profile and Defective Interferon-γ and Granzyme K in Natural Killer Cells from Systemic Juvenile Idiopathic Arthritis Patients.” ARTHRITIS & RHEUMATOLOGY 69 (1): 213–24. https://doi.org/10.1002/art.39933.
Chicago author-date (all authors)
Put, Karen, Jessica Vandenhaute, Anneleen Avau, Annemarie van Nieuwenhuijze, Ellen Brisse, Tim Dierckx, Omer Rutgeerts, Josselyn E Garcia-Perez, Jaan Toelen, Mark Waer, Georges Leclercq, An Goris, Johan Van Weyenbergh, Adrian Liston, Lien De Somer, Carine H Wouters, and Patrick Matthys. 2017. “Inflammatory Gene Expression Profile and Defective Interferon-γ and Granzyme K in Natural Killer Cells from Systemic Juvenile Idiopathic Arthritis Patients.” ARTHRITIS & RHEUMATOLOGY 69 (1): 213–224. doi:10.1002/art.39933.
Vancouver
1.
Put K, Vandenhaute J, Avau A, van Nieuwenhuijze A, Brisse E, Dierckx T, et al. Inflammatory gene expression profile and defective interferon-γ and granzyme K in natural killer cells from systemic juvenile idiopathic arthritis patients. ARTHRITIS & RHEUMATOLOGY. 2017;69(1):213–24.
IEEE
[1]
K. Put et al., “Inflammatory gene expression profile and defective interferon-γ and granzyme K in natural killer cells from systemic juvenile idiopathic arthritis patients,” ARTHRITIS & RHEUMATOLOGY, vol. 69, no. 1, pp. 213–224, 2017.
@article{8507155,
  abstract     = {{Objective: Systemic juvenile idiopathic arthritis (JIA) is an immunoinflammatory disease characterized by arthritis and systemic manifestations. The role of natural killer (NK) cells in the pathogenesis of systemic JIA remains unclear. The purpose of this study was to perform a comprehensive analysis of NK cell phenotype and functionality in patients with systemic JIA. 
Methods: Transcriptional alterations specific to NK cells were investigated by RNA sequencing of highly purified NK cells from 6 patients with active systemic JIA and 6 age-matched healthy controls. Cytokines (NK cell-stimulating and others) were quantified in plasma samples (n=18). NK cell phenotype and cytotoxic activity against tumor cells were determined (n=10), together with their interferon-gamma (IFN gamma)-producing function (n=8). 
Results: NK cells from the systemic JIA patients showed an altered gene expression profile compared to cells from the healthy controls, with enrichment of immunoinflammatory pathways, increased expression of innate genes including TLR4 and S100A9, and decreased expression of immune-regulating genes such as IL10RA and GZMK. In the patients' plasma, interleukin-18 (IL-18) levels were increased, and a decreased ratio of IFN gamma to IL-18 was observed. NK cells from the patients exhibited specific alterations in the balance of inhibitory and activating receptors, with decreased killer cell lectin-like receptor G1 and increased NKp44 expression. Although NK cells from the patients showed increased granzyme B expression, consistent with intact cytotoxicity and degranulation against a tumor cell line, decreased granzyme K expression in CD56(bright) NK cells and defective IL-18-induced IFN gamma production and signaling were demonstrated. 
Conclusion: NK cells are active players in the inflammatory environment typical of systemic JIA. Although their cytotoxic function is globally intact, subtle defects in NK-related pathways, such as granzyme K expression and IL-18-driven IFN gamma production, may contribute to the immunoinflammatory dysregulation in this disease.}},
  author       = {{Put, Karen and Vandenhaute, Jessica and Avau, Anneleen and van Nieuwenhuijze, Annemarie and Brisse, Ellen and Dierckx, Tim and Rutgeerts, Omer and Garcia-Perez, Josselyn E and Toelen, Jaan and Waer, Mark and Leclercq, Georges and Goris, An and Van Weyenbergh, Johan and Liston, Adrian and De Somer, Lien and Wouters, Carine H and Matthys, Patrick}},
  issn         = {{2326-5191}},
  journal      = {{ARTHRITIS & RHEUMATOLOGY}},
  keywords     = {{MACROPHAGE ACTIVATION SYNDROME,HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS,RHEUMATOID-ARTHRITIS,MULTIPLE-SCLEROSIS,PERIPHERAL-BLOOD,IL-1 BLOCKADE,PATHOGENESIS,DYSFUNCTION,INTERLEUKIN-18,CYTOKINES}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{213--224}},
  title        = {{Inflammatory gene expression profile and defective interferon-γ and granzyme K in natural killer cells from systemic juvenile idiopathic arthritis patients}},
  url          = {{http://doi.org/10.1002/art.39933}},
  volume       = {{69}},
  year         = {{2017}},
}

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