Natural Killer Cell Subsets and Their Functional Activity in Behçet’s Disease

Coşan, Fulya; Çetin, Esin Aktaş; Akdeniz, Nilgün; Emrence, Zeliha; Çefle, Ayşe; Deniz, Günnur

doi:10.1080/08820139.2017.1288240

Cited by 27 publications

(18 citation statements)

References 40 publications

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“…NK cells have recently been reported to play an important role in Th1 dominance in BD patients, and the Th1-type cytokine IFN-γ is known to inhibit Th17 cells from producing cytokine IL-17 (27). Cosan et al reported an advantage of the NK1 subset, but compared with healthy subjects, the proportions of NK2, NK17, and IL-10-secreting cells in BD patients were lower, and similar cytokine profiles have been observed in BD patients with mucosal skin involvement (28). Because of the inhibitory effect of IFN-γ, the dominant function of NK1 cells was increased, and increased secretion of IFN-γ may inhibit NK2, NK17, and NKreg cells in BD patients.…”

Section: The Role Of Innate Immune Cells In the Pathogenesis Of Behcementioning

confidence: 90%

Immunopathogenesis of Behcet's Disease

et al. 2019

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Behcet's disease (BD) is a chronic systemic inflammatory vasculitis of unknown etiology characterized by recurrent episodes of oral aphthous ulcers, genital ulcers, skin lesions, ocular lesions, and other manifestations. Although the pathogenesis of BD is unclear, some studies have shown that immunological aberrations play an important role in the development and progression of BD. Infection-related trigger factors, including antigens and autoantigens, are believed to mediate the development of BD in patients with a genetic predisposition and subsequently activate the innate and adaptive immune systems, resulting in the production of numerous cytokines and chemokines to combat the infection-related factors. The study of the immunological mechanism of BD paves the way for the development of innovative therapies. Recently, novel biotherapy approaches, including interferon-α (IFN-α), tumor necrosis factor-α (TNF-α) antagonists, and other agents that target interleukins and their receptors, have shown promising results in the treatment of patients with refractory BD and have improved the prognosis of BD. In this review, we provide the current concepts of BD immunopathogenesis.

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Section: The Role Of Innate Immune Cells In the Pathogenesis Of Behcementioning

confidence: 90%

Immunopathogenesis of Behcet's Disease

et al. 2019

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“…In BD patients with mucocutaneous involvement, the cytotoxic activity of the NK cells remained unchanged and there was no significant change in CD107a expression compared to healthy individuals. There was also no significant difference between patients that had frequent oral ulcers and rare oral ulcers ( 125 ). In heterogeneous groups of BD patients, CD107a expression of total NK cells were found to be upregulated when compared to healthy individuals ( 144 , 148 ).…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 91%

“…Current studies demonstrated that these changes in NK cells were probably dependent on the organ involvement. BD patients with arthritis had decreased numbers of NK cells in their blood and synovial fluid compared to healthy controls and AS patients ( 142 ), while there was no such a change in NK cells and their subsets (CD16 bright CD56 dim and CD16 dim CD56 bright cells) in mucocutaneous BD patients during the active phase of the diseases compared to healthy controls and remission phase ( 125 ). Two studies with heterogeneous groups of BD patients demonstrated an increase in the numbers of cytokine secreting NK cells ( 143 , 144 ), while one of them also demonstrated a decline in the numbers of cytotoxic NK cells ( 144 ).…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 96%

“…In BD, IL-12 secreted by Th1 cells activates NK cells, induces their migration to the site of inflammation and contributes to tissue damage in these patients ( 153 ). IFN-γ-secreting NK1 cells were increased in BD patients with mucocutaneous involvement, while the number of the other NK subsets (NK2, NK17 cells, and IL-10-secreting regulatory NK cell subsets) are decreased in these patients ( 125 ). A similar NK1 predominated cytokine secretion pattern was also observed among CD56 bright NK cells in a more heterogeneous group of BD patients which confirms the above-mentioned observation ( 144 ).…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 98%

“…A small fraction of NK cells was revealed to limit antigen specific T cell proliferation in vitro in IL-10 dependent manner, which was termed as regulatory NK (NKreg) cells ( 8 ). A number of studies also proposed regulatory roles for NK cells, either by production of IL-10 or by counter-balancing the ongoing inflammation ( 125 – 127 ).…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 99%

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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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Disease Mechanisms

Direşkeneli

Saruhan‐Direskeneli

2019

Behçet Syndrome

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Natural Killer Cell Subsets and Their Functional Activity in Behçet’s Disease

Cited by 27 publications

References 40 publications

Immunopathogenesis of Behcet's Disease

Immunopathogenesis of Behcet's Disease

The Role of Natural Killer Cells in Autoimmune Diseases

Disease Mechanisms

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