NK cells: elusive players in autoimmunity

Johansson, Sofia; Berg, Louise; Hall, Håkan; Höglund, Petter

doi:10.1016/j.it.2005.08.008

Cited by 104 publications

(83 citation statements)

References 69 publications

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“…The role of NK cells in autoimmune diabetes remains controversial (8). On one hand, NK cells exhibit a pathogenic function in the last stage of diabetes in diabetes model induced by anti-CTLA-4 Ab (14).…”

Section: Discussionmentioning

confidence: 99%

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NK3-Like NK Cells Are Involved in Protective Effect of Polyinosinic-Polycytidylic Acid on Type 1 Diabetes in Nonobese Diabetic Mice

Zhou

Wei

Tian

2007

The Journal of Immunology

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Type 1 diabetes in NOD mice is characterized by the uncontrolled Th1 immune responses and deficiency of regulatory or suppressor cells. Previous study has shown that NOD mice treated with polyinosinic-polycytidylic acid (poly(I:C)) have a markedly reduced incidence of diabetes, but the underlying mechanisms remain unclear. In this study, we report that the prevention of diabetes by poly(I:C) is associated with the formation of Th2-enriched environment in spleen and pancreas. We further show that the prevention of diabetes and the formation of Th2-enriched environment depend on the presence of NK cells. Long-term poly(I:C)-treated NK cells exhibit a NK3-like phenotype, and are involved in the induction of Th2 bias of spleen cells in response to islet autoantigens via TGF-β-dependent manner. Therefore, NK cells mediate the protective effect of poly(I:C) possibly through the promotion of Th2 bias of immune responses. These findings suggest that NK cells can participate in the regulation of autoimmune diabetes.

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Section: Discussionmentioning

confidence: 99%

“…Increasing evidence from human autoimmune diseases and animal models suggests the involvement of NK cells in immunoregulation or pathogenesis of autoimmune diseases (7,8). However, the role of NK cells in T1D remains obscure.…”

Section: Nk3-like Nk Cells Are Involved In Protective Effectmentioning

confidence: 99%

NK3-Like NK Cells Are Involved in Protective Effect of Polyinosinic-Polycytidylic Acid on Type 1 Diabetes in Nonobese Diabetic Mice

Zhou

Wei

Tian

2007

The Journal of Immunology

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“…40 The expression of KIR on the Tcell effector subsets in IBD has yet to be assessed. KIRs are predominantly expressed on NK cells, lymphocytes which have been found to produce both protective and detrimental effects in autoimmune conditions (reviewed by Johansson et al 41 ), although the potential role of NK cells in the development of IBD has been largely overlooked by investigators. However, several studies have reported reduced cytotoxicity of peripheral blood NK cells from UC patients.…”

Section: Discussionmentioning

confidence: 99%

Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

et al. 2006

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Killer immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon binding with the appropriate human leucocyte antigen (HLA) ligand on target cells. Recent genetic association studies have implicated KIR genotype in the development of several inflammatory conditions. Ulcerative colitis (UC) is an inflammatory disorder of the colonic mucosa that results from an inappropriate activation of the immune system driven by host bacterial flora. We developed a polymerase chain reaction-sequence specific primer (SSP)-based assay to genotype 194 UC patients and 216 control individuals for 14 KIR genes, the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. Initial analysis found the phenotype frequency of KIR2DL2 and -2DS2 to be significantly increased in the UC cohort (P ¼ 0.030 and 0.038, respectively). Logistic regression analysis revealed a protective effect conferred by KIR2DL3 in the presence of its ligand HLA-Cw group 1 (P ¼ 0.019). These results suggest that KIR genotype and HLA ligand interaction may contribute to the genetic susceptibility of UC.

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“…[9][10][11] Cytotoxicity of NK cells from NOD mice against NK-sensitive tumor cell targets is lower than the killing activity from NK cells of nondiabetic mice. 12 In particular, Johansson et al 9 showed defective killing triggered by FcR and Ly49D activating receptors in NOD mice. Similarly, impaired NKG2D modulation in NOD mice has recently been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome

et al. 2008

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The mouse Ly49 and human killer cell immunoglobulin-like receptors (KIR) gene clusters encode activating and inhibitory class I MHC receptors on natural killer (NK) cells. A direct correlation between the presence of multiple activating KIR and various human autoimmune diseases including diabetes has been shown. Previous studies have implicated NK cell receptors in the development of diabetes in the non-obese diabetic (NOD) inbred mouse strain. To assess the contribution of Ly49 to NOD disease acceleration the Ly49 gene cluster of these mice was sequenced. Remarkably, the NOD Ly49 haplotype encodes the largest haplotype and the most functional activating Ly49 of any known mouse strain. These activating Ly49 include three Ly49p-related and two Ly49h-related genes. The NOD cluster contains large regions highly homologous to both C57BL/6 and 129 haplotypes, suggesting unequal crossing over as a mechanism of Ly49 haplotype evolution. Interestingly, the 129-like region has duplicated in the NOD genome. Thus, the NOD Ly49 cluster is a unique mix of elements seen in previously characterized Ly49 haplotypes resulting in a disproportionately large number of functional activating Ly49 genes. Finally, the functionality of activating Ly49 in NOD mice was confirmed in cytotoxicity assays.

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NK cells: elusive players in autoimmunity

Cited by 104 publications

References 69 publications

NK3-Like NK Cells Are Involved in Protective Effect of Polyinosinic-Polycytidylic Acid on Type 1 Diabetes in Nonobese Diabetic Mice

NK3-Like NK Cells Are Involved in Protective Effect of Polyinosinic-Polycytidylic Acid on Type 1 Diabetes in Nonobese Diabetic Mice

Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome

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