NK Cells and Type 1 Diabetes

Rodacki, Melanie; Milech, Adolpho; Oliveira, José Egídio Paulo de

doi:10.1080/17402520600877182

Cited by 48 publications

(29 citation statements)

References 49 publications

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“…More recently, a larger study confirmed a functional impairment of NK cells in T1D patients, i.e., reduced surface expression of activating receptors and low levels of IFN-and perforin, and suggested that these alterations may be a consequence of T1D, since they are evident exclusively in long-standing disease [359]. It has also been reported that activated NK cells in T1D patients display a reduced expression of NKG2D receptor [357]. It is possible that a downregulation of NKG2D receptor mediates the increased risk for T1D associated with polymorphisms of MHC class I chain-related (MIC) proteins [360] that are NKG2D natural ligands.…”

Section: T Cellsmentioning

confidence: 57%

“…Increased levels of 'Th1 cell'-derived chemokines CCl3, CCl4, and CXCl10 [354,355] and of adhesion molecules ICAM and L-selectin (CD62L) [356] have been found in serum of T1D patients. Several reports have addressed NK population in the peripheral blood of T1D patients [357] and have described a decrease in the peripheral frequency, in most cases temporally related to disease onset [4,281], or a functional deficit [358], but these findings have not been universally replicated [357]. More recently, a larger study confirmed a functional impairment of NK cells in T1D patients, i.e., reduced surface expression of activating receptors and low levels of IFN-and perforin, and suggested that these alterations may be a consequence of T1D, since they are evident exclusively in long-standing disease [359].…”

Section: T Cellsmentioning

confidence: 99%

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Immunology of β-Cell Destruction

Torre

Lernmark

2010

Advances in Experimental Medicine and Biology

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Section: T Cellsmentioning

confidence: 57%

Section: T Cellsmentioning

confidence: 99%

Immunology of β-Cell Destruction

Torre

Lernmark

2010

Advances in Experimental Medicine and Biology

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“…Natural killer cells, a subtype of leukocyte, are known to play an important role in beta-cell destruction and the patho- genesis of diabetes (18). There was a significant increase in natural killer-related genes (KIR2DL4, KLRD1, KLRF1, and NKG7) in response to glucose ingestion, indicating their roles in the pathogenesis of diabetes (Fig.…”

Section: Discussionmentioning

confidence: 92%

Human transcriptome analysis of acute responses to glucose ingestion reveals the role of leukocytes in hyperglycemia-induced inflammation

Choi

Yun

Kang

et al. 2012

Physiological Genomics

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BG. Human transcriptome analysis of acute responses to glucose ingestion reveals the role of leukocytes in hyperglycemia-induced inflammation. Physiol Genomics 44: 1179 -1187, 2012. First published October 16, 2012 doi:10.1152/physiolgenomics.00179.2011.-Glucose ingestion-induced hyperglycemia has been known to induce inflammation, which is related to the pathogenesis of diabetic complications. To examine acute gene expression responses to physiological oral glucose ingestion in human circulating leukocytes, we conducted a microarray study of human circulating leukocytes sampled before, 1 h after, and 2 h after glucose ingestion in community-based participants without previous histories of diabetes (n ϭ 60). Ingestion of 75 g glucose successfully induced acute hyperglycemia (glucose concentration 91.6 Ϯ 5.3 mg/dl for fasting and 180.7 Ϯ 48.5 mg/dl for 1 h after glucose ingestion). Oral glucose ingestion significantly increased the expressions of 23 genes and decreased the expressions of 13 genes [false discovery rate (FDR) P value Ͻ0.05]. These genes are significantly involved in immunity by way of natural killer cell-mediated immunity, granulocyte-mediated immunity, and the cytokine-mediated signaling pathway (FDR P value Ͻ0.05). The present study demonstrated 36 genes that showed acute gene expression change in human leukocytes within 1 h after glucose ingestion, suggesting that leukocytes participate in the inflammatory process induced by acute hyperglycemia. We believe that these results will provide some basic insight into the role of leukocytes in hyperglycemia-induced inflammation and the pathogenesis of diabetic complications.

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“…In addition to their role in antimicrobial, antiviral, and antitumor immunity, NK cells have recently also been implicated in inflammatory and autoimmune disorders such as type I diabetes (9,10) and multiple sclerosis (11,12). Genetic variations that influence the proportion of NK cells may also contribute to the clinical outcomes in these diseases.…”

mentioning

confidence: 99%

A 17q12 Allele Is Associated with Altered NK Cell Subsets and Function

Xia

Lian

Berger

et al. 2012

The Journal of Immunology

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NK cells play an important role in innate immunity. A previous genome-wide association study demonstrated an association between a 17q12 allele (rs9916629C) and lower frequency of CD3−CD56+ NK cells in peripheral blood. We performed an analysis that not only replicates the original result of the genome-wide association study (p = 0.036) but also defines the specific cell subpopulations and functions that are modulated by the rs9916629 polymorphism in a cohort of 96 healthy adult subjects using targeted multiparameter flow cytometric profiling of NK cell phenotypes and functions. We found that rs9916629C is associated with alterations in specific NK cell subsets, including lower frequency of predominantly cytotoxic CD56dim NK cells (p = 0.011), higher frequency of predominantly regulatory CD56bright NK cells (p = 0.019), and a higher proportion of NK cells expressing the inhibitory NKG2A receptor (p = 0.0002). Functionally, rs9916629C is associated with decreased secretion of macrophage inflammatory protein-1β by NK cells in the context of Ab-dependent cell-mediated cytotoxicity (p = 0.039) and increased degranulation in response to MHC class I-deficient B cells (p = 0.017). Transcriptional profiling of NK cells suggests that rs9916629 influences the expression of transcription factors such as TBX21, which has a role in NK cell differentiation, offering a possible mechanism for the phenotypic and functional differences between the different alleles. The rs9916629C allele therefore has a validated effect on the proportion of NK cells in peripheral blood and skews NK cells toward a specific phenotypic and functional profile, potentially influencing the impact that these innate immune cells have on infection and autoimmunity.

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NK Cells and Type 1 Diabetes

Cited by 48 publications

References 49 publications

Immunology of β-Cell Destruction

Immunology of β-Cell Destruction

Human transcriptome analysis of acute responses to glucose ingestion reveals the role of leukocytes in hyperglycemia-induced inflammation

A 17q12 Allele Is Associated with Altered NK Cell Subsets and Function

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