NOD mice and autoimmunity

Aoki, Christopher A.; Borchers, Andrea T.; Ridgway, William M.; Keen, Carl L.; Ansari, Aftab A.; Gershwin, M. Eric

doi:10.1016/j.autrev.2005.02.002

Cited by 94 publications

(92 citation statements)

References 38 publications

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“…These include impaired negative selection of autoreactive T cells in the thymus, defective apoptosis of effector T cells, and reduced number and function of regulatory T cells [38][39][40]. This model provides a good framework for determining which of these immunoregulatory defects increases susceptibility of NOD mice to develop autoimmune lacrimal keratoconjunctivitis and it may provide clues regarding susceptibility factors for development of Sjögren's syndrome in humans.…”

Section: Discussionmentioning

confidence: 99%

Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

Yoon

Paiva

et al. 2008

Journal of Autoimmunity

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The non-obese diabetic (NOD) mouse is prone to develop autoimmune disease, including Sjögren's syndrome. The purpose of this study was to determine if desiccating environmental stress exacerbates the development of Sjögren's syndrome-like lacrimal keratoconjunctivitis in the NOD.B10.H2 b mouse. Four-week-old male mice were used as young controls. Sixteen-week-old male mice were untreated or subjected to desiccating stress with a fan alone or with a fan plus subcutaneous injections of the anticholinergic agent scopolamine for 5 or 10 days to inhibit tear production. Mice spontaneously developed Sjögren's syndrome-like lacrimal keratoconjunctivitis as they aged. Desiccating stress increased CD4+ and CCR5+ cells and decreased CD8+ cells in the conjunctival epithelium and lacrimal gland. Intraepithelial γδ T cells significantly decreased after 5 days and returned to baseline levels after 10 days in both groups exposed to desiccating stress. These immunopathological changes were accompanied by a decrease in conjunctival goblet cell density. Greater matrix metalloproteinase-9 production, gelatinase activity and loss of epithelial cell membrane CD25 immunoreactivity was noted in the ocular surface epithelia of stressed mice. These findings indicate that desiccating environmental stress aggravates Sjögren's syndrome-like lacrimal keratoconjunctivitis in the NOD mouse which has defective immunoregulation.

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Section: Discussionmentioning

confidence: 99%

Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

Yoon

Paiva

et al. 2008

Journal of Autoimmunity

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“…1 Much of our understanding of T1D has come from the study of disease in the nonobese diabetic (NOD) mouse. 2,3 In addition to being a model of spontaneous T1D, NOD mice spontaneously develop other tissue-related autoimmune responses. 2,4 Several genetic loci have been associated with susceptibility and development of diabetes in both humans and NOD mice.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 In addition to being a model of spontaneous T1D, NOD mice spontaneously develop other tissue-related autoimmune responses. 2,4 Several genetic loci have been associated with susceptibility and development of diabetes in both humans and NOD mice. 5 Multiple candidate genes have been identified that contribute to the genetic susceptibility of NOD mice to autoimmune diseases, including MHC class II, Il2 and Ctla4.…”

Section: Introductionmentioning

confidence: 99%

“…5 Multiple candidate genes have been identified that contribute to the genetic susceptibility of NOD mice to autoimmune diseases, including MHC class II, Il2 and Ctla4. 2,3 Natural killer (NK) cells are large granular lymphocytes that are able to lyse virally-infected and transformed cells. 6 Interestingly, several NK anomalies have been linked with diabetes.…”

Section: Introductionmentioning

confidence: 99%

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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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“…Studies of the NOD mouse, a model of spontaneous T1D, have demonstrated that autoaggressive CD4 and CD8 T cells mediate b-cell destruction (2). Although the precise factors responsible for initiating pathogenesis are unknown, it has been proposed that defects in T and B lymphocyte selection (central tolerance) and regulatory lymphocyte function (peripheral tolerance) involving FOXP3-expressing CD4 T cells, NKT cells, and NK cells underlie the development of T1D (3)(4)(5). Moreover, investigations of the NOD mouse suggest that NKT cells play a pivotal role in the development of T1D (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

NKT Cells Are Required for Complete Freund’s Adjuvant-Mediated Protection from Autoimmune Diabetes

Lee

Elzen

Tan

et al. 2011

The Journal of Immunology

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Autoimmune diabetes in NOD mice can be prevented by application of Ags derived from Mycobacterium tuberculosis in the form of bacillus Calmette-Guérin or CFA. Disease protection by CFA is associated with a reduction in the numbers of pathogenic β-cell specific, self-reactive CTLs, a phenomenon dependent on the presence and function of NK cells. However, the mechanisms by which NK cells are activated and recruited by heat-killed M. tuberculosis within CFA are unclear. In this study, we report that CFA-mediated NK cell activation and mobilization is dependent on CD1d expression. The administration of M. tuberculosis from CFA results in rapid NKT cell activation and IFN-γ secretion both in vitro and in vivo. CFA-induced NKT cell activation is intact in MyD88−/− mice suggesting that the mechanism is independent of TLR signaling. Furthermore, CD1d expression was found to be essential for both M. tuberculosis-triggered NKT cell activation and CFA-mediated protection of NOD mice from diabetes. Collectively, these findings reveal hitherto previously unidentified roles for NKT cells in the adjuvant-promoting effects of CFA on innate and adaptive immunity.

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NOD mice and autoimmunity

Cited by 94 publications

References 38 publications

Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

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

NKT Cells Are Required for Complete Freund’s Adjuvant-Mediated Protection from Autoimmune Diabetes

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