Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls

Elemam, Noha Mousaad; Hachim, Mahmood Yaseen; Hannawi, Suad; Maghazachi, Azzam A.

doi:10.3390/genes11050492

Cited by 17 publications

(13 citation statements)

References 63 publications

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“…Despite their increased ratios in inflamed synovium, NK cells have been shown to be decreased in peripheral blood samples of RA patients when compared with that of healthy subjects ( 265 , 266 ). Additionally, it has been demonstrated in a study that activated NK cells were decreased in peripheral blood of RA patients compared to healthy subjects whereas the frequency of resting NK cells was not altered ( 267 ). These findings suggest that activated NK cells might be infiltrated to the inflamed synovium of RA patients.…”

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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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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“…Another study identified differentially expressed genes in NK cells obtained from RA patients versus healthy controls. NK cells isolated from patients with RA expressed higher mRNA levels of CD56, CXCL16, PECAM-1, ITGB7, BTK, TLR10, and IL-1β, but lower levels of CCL2, CCR4, RELA and IBTK [ 57 ]. Yamin et al.…”

Section: The Role Of Nk Cells In Ramentioning

confidence: 99%

Innate immunity drives pathogenesis of rheumatoid arthritis

2021

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Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1% of the general population. This disease is characterized by persistent articular inflammation and joint damage driven by the proliferating synovial tissue fibroblasts as well as neutrophil, monocyte and lymphocyte trafficking into the synovium. The factors leading to RA pathogenesis remain poorly elucidated although genetic and environmental factors have been proposed to be the main contributors to RA. The majority of the early studies focused on the role of lymphocytes and adaptive immune responses in RA. However, in the past two decades, emerging studies showed that the innate immune system plays a critical role in the onset and progression of RA pathogenesis. Various innate immune cells including monocytes, macrophages and dendritic cells are involved in inflammatory responses seen in RA patients as well as in driving the activation of the adaptive immune system, which plays a major role in the later stages of the disease. Here we focus the discussion on the role of different innate immune cells and components in initiation and progression of RA. New therapeutic approaches targeting different inflammatory pathways and innate immune cells will be highlighted here. Recent emergence and the significant roles of innate lymphoid cells and inflammasomes will be also discussed.

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“…Single-nucleotide polymorphisms in NK cell-related genesespecially NKG2D and MHC class I polypeptide-related sequence A (MICA)-were shown to be associated with RA susceptibility and severity (104)(105)(106)(107). Early studies reported conflicting findings regarding the roles of NK cells in RA, which may be attributable to the fact that peripheral but not local synovial NK cells were examined; moreover, the different NK subsets were not distinguished, and the data were derived from different cohorts (108)(109)(110).…”

Section: Nk Cells and Rheumatoid Arthritis (Ra)mentioning

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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Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls

Cited by 17 publications

References 63 publications

The Role of Natural Killer Cells in Autoimmune Diseases

The Role of Natural Killer Cells in Autoimmune Diseases

Innate immunity drives pathogenesis of rheumatoid arthritis

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

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