Immunohistochemical investigation demonstrated an increased cytok

Immunohistochemical investigation demonstrated an increased cytokine production, including interleukin (IL)-1α, IL-1β, IL-2, IL-3, IL-6, and tumour necrosis factor (TNF)-α in senile plaques in the hippocampus and cortex of Alzheimer’s brain [3]. Microglia and astrocytes can produce cytotoxic molecules and these pro-inflammatory cytokines [5]. The presence of peripheral monocytes/macrophages within the central nervous system (CNS) can reduce the extension of β-amyloid plaques

MAPK inhibitor via multiple mechanisms regulated by immune system [5]. Although the attempts for clarifying the environmental aetiology of AD have been hopeless, however, many researchers have demonstrated an increased risk among those people HDAC inhibitor with a family history of AD [6]. Diversity of risk factors for sporadic AD has shown that it is a multifactorial

disease [2]. Natural killer (NK) cells are granular lymphocytes and play an important role in the immune system [7]. Involvement of NK cells in some neurodegenerative diseases such as multiple sclerosis (MS) has been well studied [8]. A decreased NK cell activity has been reported in AD patients [9], which may suggest that NK cells may also contribute in AD immunopathogenesis. However, the role of NK cells in AD patients is not well studied and requires to more investigation. In this paper, we tried to review the data resulting from different studies regarding the role of NK cells in AD. Natural killer (NK) cells were defined by their ability to spontaneously kill tumour cells and virally infected cells [10, 11]. These cells are derived from hematopoietic stem cells in the bone marrow (BM). Moreover, the development of NK cells in other organs such as liver and thymus have also been reported [12]. Peripheral activation of NK cells may lead to phenotype modification and modulation of NK cell functions [13]. In humans, NK cells have been phenotypically defined as CD3−CD56+ lymphocytes that may be further subdivided into CD56dimCD16bright Immune system (90% of all NK) and CD56brightCD16− cells. These subpopulations differ based on cytotoxic capacity

and cytokine production [14]. NK cells main functions are destroying a wide variety of target cells or production of cytokines [15] (Fig. 1). NK cells destroy the target cells by perforin and granzymes, which are stored in cytoplasmic granules and released upon activation [16]. NK cells also express TNF-related apoptosis-inducing ligand (TRAIL) and FasL, which are important mediators of apoptosis. Notably, cytokine production by NK cells can be regulated through both activating and inhibitory receptors. Hence, NK cells may have both immunostimulatory and immunomodulatory effects through production of cytokines such as interferon (IFN)-γ, TNF-α, granulocyte monocyte colony-stimulating factor (GM-CSF), IL-5, IL-13, IL-10 and transforming growth factor (TGF)-β.

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