scholarly journals AB0178 Phenotyping of natural killer (NK) receptors on NK and NKT-LIKE cells discloses defective immune-regulatory capability in patients with systemic sclerosis

2017 ◽  
Author(s):  
M Cossu ◽  
L Beretta ◽  
E Trombetta ◽  
STA van Bijnen ◽  
M Rossato ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Natural Killer ◽  
Nk Receptors

scholarly journals Natural Killer Cells: Potential Biomarkers and Therapeutic Target in Autoimmune Diseases?

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Gianchecchi ◽  
Domenico V. Delfino ◽  
Alessandra Fierabracci
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Cytotoxic Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell

Autoimmune diseases recognize a multifactorial pathogenesis, although the exact mechanism responsible for their onset remains to be fully elucidated. Over the past few years, the role of natural killer (NK) cells in shaping immune responses has been highlighted even though their involvement is profoundly linked to the subpopulation involved and to the site where such interaction takes place. The aberrant number and functionality of NK cells have been reported in several different autoimmune disorders. In the present review, we report the most recent findings regarding the involvement of NK cells in both systemic and organ-specific autoimmune diseases, including type 1 diabetes (T1D), primary biliary cholangitis (PBC), systemic sclerosis, systemic lupus erythematosus (SLE), primary Sjögren syndrome, rheumatoid arthritis, and multiple sclerosis. In T1D, innate inflammation induces NK cell activation, disrupting the Treg function. In addition, certain genetic variants identified as risk factors for T1D influenced the activation of NK cells promoting their cytotoxic activity. The role of NK cells has also been demonstrated in the pathogenesis of PBC mediating direct or indirect biliary epithelial cell destruction. NK cell frequency and number were enhanced in both the peripheral blood and the liver of patients and associated with increased NK cell cytotoxic activity and perforin expression levels. NK cells were also involved in the perpetuation of disease through autoreactive CD4 T cell activation in the presence of antigen-presenting cells. In systemic sclerosis (SSc), in addition to phenotypic abnormalities, patients presented a reduction in CD56hi NK-cells. Moreover, NK cells presented a deficient killing activity. The influence of the activating and inhibitory killer cell immunoglobulin-like receptors (KIRs) has been investigated in SSc and SLE susceptibility. Furthermore, autoantibodies to KIRs have been identified in different systemic autoimmune conditions. Because of its role in modulating the immune-mediated pathology, NK subpopulation could represent a potential marker for disease activity and target for therapeutic intervention.

scholarly journals Invariant natural killer T cells are functionally impaired in patients with systemic sclerosis

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Ann-Christin Pecher ◽  
Felix Kettemann ◽  
Elisa Asteriti ◽  
Hannes Schmid ◽  
Silke Duerr-Stoerzer ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Natural Killer ◽  
Immunosuppressive Drugs ◽  
Healthy Controls ◽  
Inkt Cells ◽  
Novel Approach ◽  
Functionally Impaired ◽  
Transfer Strategies ◽  
Invariant Natural Killer ◽  
Natural Killer T

Abstract Background Systemic sclerosis (SSc) is a potentially fatal autoimmune disease that leads to extensive fibrosis of the skin and internal organs. Invariant natural killer T (iNKT) cells are potent immunoregulatory T lymphocytes being able to orchestrate dysregulated immune responses. The purpose of this study was to evaluate numbers and function of iNKT cells in patients with SSc and to analyze their correlation with disease parameters. Methods Human iNKT cells from 88 patients with SSc and 33 healthy controls were analyzed by flow cytometry. Their proliferative capacity and cytokine production were investigated following activation with CD1d ligand α-galactosylceramide (α-GalCer). Results We observed an absolute and relative decrease of iNKT cells in patients with SSc compared with healthy controls. Interestingly, the subtype of SSc, disease severity, or treatment with immunosuppressive drugs did not affect iNKT cell numbers. However, T helper (Th) cell immune polarization was biased towards a Th17 immunophenotype in SSc patients. Moreover, iNKT cells from patients with SSc showed a significantly decreased expansion capacity upon stimulation with α-GalCer. Conclusion iNKT cells are deficient and functionally impaired in patients with SSc. Therefore, adoptive transfer strategies using culture-expanded iNKT cells could be a novel approach to treat SSc patients.

scholarly journals T-cells expressing natural killer (NK) receptors are altered in multiple sclerosis and responses to α-galactosylceramide are impaired

2008 ◽  
Vol 275 (1-2) ◽  
pp. 22-28 ◽  
Author(s):  
Joan O'Keeffe ◽  
Carol M. Gately ◽  
Timothy Counihan ◽  
Michael Hennessy ◽  
Teresa Leahy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Natural Killer ◽  
Nk Receptors

Lack of Natural Killer Cell Augmentation in vitro by Human Interferon Gamma in a Subset of Patients with Systemic Sclerosis

Pathobiology ◽  
1995 ◽  
Vol 63 (5) ◽  
pp. 288-292 ◽  
Author(s):  
A. Wanchu ◽  
V.K. Singh ◽  
V.S. Yadav ◽  
S. Biswas ◽  
R. Misra ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Interferon Gamma ◽  
Killer Cell ◽  
Human Interferon

scholarly journals Lymphokine-activated killer cell and natural killer cell activities in patients with systemic sclerosis

1992 ◽  
Vol 35 (6) ◽  
pp. 694-699 ◽  
Author(s):  
Thomas V. Kantor ◽  
Theresa L. Whiteside ◽  
Diana Friberg ◽  
Robert B. Buckingham ◽  
Thomas A. Medsger
Keyword(s):  
Systemic Sclerosis ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Killer Cell ◽  
Lymphokine Activated Killer Cell

scholarly journals FRI0408 Invariant natural killer t cells in systemic sclerosis

2018 ◽  
Author(s):  
A.-C. Pecher ◽  
F. Kettemann ◽  
J. Henes ◽  
S. Duerr-Stoerzer ◽  
C. Schneidawind ◽  
...  
Keyword(s):  
T Cells ◽  
Systemic Sclerosis ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

scholarly journals Cytometric Characterization of Main Immunocompetent Cells in Patients with Systemic Sclerosis: Relationship with Disease Activity and Type of Immunosuppressive Treatment

2019 ◽  
Vol 8 (5) ◽  
pp. 625 ◽  
Author(s):  
Olga Gumkowska-Sroka ◽  
Krystyna Jagoda ◽  
Aleksander Owczarek ◽  
Grzegorz Helbig ◽  
Joanna Giemza-Stokłosa ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Disease Activity ◽  
Natural Killer ◽  
Immune Cell ◽  
Immunosuppressive Treatment ◽  
Double Positive ◽  
Nkt Cell ◽  
Organ Fibrosis ◽  
Cell Profile

Systemic sclerosis (SSc) is a connective tissue disease that is characterized by widespread skin and internal organ fibrosis vasculopathy and immune response abnormalities, including T, B, natural killer (NK), and natural killer T (NKT) cell involvement. The aim of the study was to investigate the immune cell profile in patients with systemic sclerosis in relation to the disease activity, severity, and antibody presence and their relation to the type of immunosuppressive treatment. Cytometric examination identified following cell lines: B cells (Breg, B memory, B mature) and plasmablasts, T cell, T double positive—Tdp, T double negative—Tdn, NK, and NKT cell and monocytes. The disease severity and activity were assessed based on the Medsger and the EULAR Scleroderma Trials and Research Group (EUSTAR) 2017 scales respectively. In the study, SSc patients were characterized by higher total lymphocyte count parallel to increased frequency of Ts and Th cells. In SSc patients, increment of Tdp and reduction of Tdn as well as NK and NKT cells were observed. Additionally in SSc patients the reduction of B memory was noted. Head to head comparison between cyclophosphamide (CYC) and mycophenolate mofetil (MMF) treatment showed a reduction of CD19+ cells, but increment of plasmablasts in CYC treated patients.

scholarly journals Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4816-4824 ◽  
Author(s):  
Pearlie K. Epling-Burnette ◽  
Fanqi Bai ◽  
Jeffrey S. Painter ◽  
Dana E. Rollison ◽  
Helmut R. Salih ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Disease Progression ◽  
Natural Killer ◽  
Prognostic Score ◽  
Leukemic Cell ◽  
Nk Receptors ◽  
Cytolytic Function ◽  
Healthy Donors ◽  
Nk Cytotoxicity ◽  
Activating Receptor

AbstractMyelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis with potential for progression to acute myeloid leukemia (AML). We compared natural killer (NK) cytolytic function in 48 MDS patients with 37 healthy donors and found reduced activity in the patient population (K562 cytolysis, 19% ± 21% SD versus 40% ± 17%) (P < .001). NK cytotoxicity in MDS patients was reduced against 3 disparate tumor targets with differential activating receptor requirement, suggesting global defects in NK function. Reduced NK function in MDS was significantly associated with higher International Prognostic Score (P = .01), abnormal karyotype (P = .05), the presence of excess blasts (P = .01), and age-adjusted bone marrow hypercellularity (P = .04). MDS patients had a display of the activating receptor NKp30, and NKG2D down-regulation closely correlated with impaired NK function (P = .001). NKG2D ligands (MICA and MICB) were expressed on CD34+ cells from bone marrow of 30% of MDS patients and a leukemic cell line derived from an MDS patient (MDS1). Collectively, these findings suggest that impairment of NK cytolytic function derives in part from reduced activating NK receptors such as NKG2D in association with disease progression. Evasion of NK immunosurveillance may have importance for MDS disease progression.

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