The role of killer-cell immunoglobulin-like receptor (KIR) genes in susceptibility to inflammatory bowel disease: systematic review and meta-analysis

Fathollahi, Anwar; Aslani, Saeed; Mostafaei, Shayan; Rezaei, Nima; Mahmoudi, Mahdi

doi:10.1007/s00011-018-1162-7

Cited by 21 publications

(19 citation statements)

References 32 publications

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“…In this context, the actual pathogenetic role of NK cell is still undefined. KIR polymorphism and positive associations between 2DL5/2DS1 KIR and UC risk has been reported (140, 159). In active UC, peripheral NK cells were decreased significantly compared to inactive UC.…”

Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 98%

“…In this regard, the presence of killer (K) cells in mesenteric LN was described in CD patients long ago (139). The involvement of NK cells in IBD pathogenesis has been supported by a recent study on polymorphisms of killer immunoglobulin-like receptors (KIR) genes (140). KIR are NK cell surface receptors, which bind to the class I MHC and have inhibitory or activating effects on NK cells (Table 1).…”

Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 99%

“…KIR are NK cell surface receptors, which bind to the class I MHC and have inhibitory or activating effects on NK cells (Table 1). A meta-analysis of 432 UC and 1677 CD patients showed positive associations between 2DL5/2DS1 (members of KIR genes) and UC risk, and a negative association between 2DS3 and CD risk (140).…”

Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 99%

“…Of note, genetic alterations in regulatory NK cell receptors have been reported. Indeed, KIR polymorphism is implicated in susceptibility to CD (140), with a significant association of the KIR2DL3/HLA-C1 genotype and CD (142), although the cellular mechanism of this genetic contribution is poorly defined. It has been described that the “licensing” of NK cells, determined by the presence of KIR2DL3 and homozygous HLA-C1 in the host genome, results in cytokine reprogramming that permits promotion of CD4 + T cell activation and Th17 differentiation ex vivo .…”

Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 99%

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Human Gut-Associated Natural Killer Cells in Health and Disease

et al. 2019

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It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals and virus infections. The functions of NK cells in the gut are much more complex. Gut NK cells are not precisely organized in lymphoid aggregates but rather scattered in the epithelium or in the stroma, where they come in contact with a multitude of antigens derived from commensal or pathogenic microorganisms in addition to components of microbiota. Furthermore, NK cells in the bowel interact with several cell types, including epithelial cells, fibroblasts, macrophages, dendritic cells, and T lymphocytes, and contribute to the maintenance of immune homeostasis and development of efficient immune responses. NK cells have a key role in the response to intestinal bacterial infections, primarily through production of IFNγ, which can stimulate recruitment of additional NK cells from peripheral blood leading to amplification of the anti-bacterial immune response. Additionally, NK cells can have a role in the pathogenesis of gut autoimmune inflammatory bowel diseases (IBDs), such as Crohn's Disease and Ulcerative Colitis. These diseases are considered relevant to the generation of gastrointestinal malignancies. Indeed, the role of gut-associated NK cells in the immune response to bowel cancers is known. Thus, in the gut immune system, NK cells play a dual role, participating in both physiological and pathogenic processes. In this review, we will analyze the known functions of NK cells in the gut mucosa both in health and disease, focusing on the cross-talk among bowel microenvironment, epithelial barrier integrity, microbiota, and NK cells.

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Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 98%

Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 99%

Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 99%

Section: Inflammatory Bowel Disease (Ibd) and Nk Cellsmentioning

confidence: 99%

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Human Gut-Associated Natural Killer Cells in Health and Disease

et al. 2019

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“…Nevertheless, the association of KIR genes in the susceptibility for Crohn's disease and UC suggests involvement of NK cells in disease development. KIR2DL2, KIR2DS2, KIR2DL5, and KIR2DS1 were found to confer a higher UC susceptibility, whereas a negative association was found between KIR2DS3 and Crohn's disease risk (87,88). More recent reports have focused on NK cells in tissues in contrast to the peripheral circulating NK cells, resulting in the identification of organ-specific and tissueresident NK cells.…”

Section: Natural Killer Cells In Multifactorial Autoinflammatory Disementioning

confidence: 99%

Natural Killer Cells in Systemic Autoinflammatory Diseases: A Focus on Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome

2020

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Natural killer (NK) cells are innate immune lymphocytes with potent cytolytic and immune-regulatory activities. NK cells are well-known for their ability to kill infected and malignant cells in a fast and non-specific way without prior sensitization. For this purpose, NK cells are equipped with a set of cytotoxic molecules such as perforin and apoptosis-inducing proteins. NK cells also have the capacity to produce large amounts of cytokines and chemokines that synergize with their cytotoxic function and that ensure interaction with other immune cells. A less known feature of NK cells is their capacity to kill non-infected autologous cells, such as immature dendritic cells and activated T cells and monocytes. Via the release of large amounts of TNF-α and IFN-γ, NK cells may contribute to disease pathology. Conversely they may exert a regulatory role through secretion of immuno-regulatory cytokines such as GM-CSF, IL-13, and IL-10. Thus, NK cells may be important target and effector cells in the pathogenesis of autoinflammatory diseases, in particular in those disorders associated with a cytokine storm or in conditions where immune cells are highly activated. Key examples of such diseases are systemic juvenile idiopathic arthritis (sJIA) and its well-associated complication, macrophage activation syndrome (MAS). sJIA is a chronic childhood immune disorder of unknown etiology, characterized by arthritis and systemic inflammation, including a daily spiking fever and evanescent rash. MAS is a potentially fatal complication of autoimmune and autoinflammatory diseases, and most prevalently associated with sJIA. MAS is considered as a subtype of hemophagocytic lymphohistiocytosis (HLH), a systemic hyperinflammatory disorder characterized by defective cytotoxic pathways of cytotoxic T and NK cells. In this review, we describe the established features of NK cells and provide the results of a literature survey on the reported NK cell abnormalities in monogenic and multifactorial autoinflammatory disorders. Finally, we discuss the role of NK cells in the pathogenesis of sJIA and MAS.

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