NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

Simoni, Yannick; Gautron, Anne-Sophie; Beaudoin, Lucie; Bui, Linh‐Chi; Michel, Marie‐Laure; Coumoul, Xavier; Eberl, Gérard; Leite‐de‐Moraes, Maria; Lehuen, Agnès

doi:10.1002/eji.201141751

Cited by 42 publications

(44 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…indicate the involvement of NKT cells in both syngeneic and allogeneic immune rejection of islet allografts in the liver of mice and demonstrate the immunosuppressive role of adenosine in preventing NKT cell-mediated destruction of islet grafts [141]. Recently, a new subset, iNKT17 cells, that produce high levels of the pro-inflammatory cytokine IL-17 implicated in several autoimmune diseases, has been identified [142]. In the NOD mouse, the iNKT17 cells which are present in abundance, infiltrated the pancreas where they expressed IL-17 mRNA, enhancing the incidence of diabetes.…”

Section: Pathogenesis Of Type 1 Diabetes Mellitusmentioning

confidence: 99%

The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation

Chhabra¹,

Linden²,

Lobo³

et al. 2012

CDR

View full text Add to dashboard Cite

Activation of adenosine A2A receptors (A2AR) reduces inflammation by generally inhibiting the activation of pro-inflammatory cells, decreasing endothelial adhesion molecule expression and reducing the release of proinflammatory cytokine mediators. Numerous preclinical studies using selective A2AR agonists, antagonists, A2AR knockout as well as chimeric mice have suggested the therapeutic potential of A2AR agonists for the treatment of ischemia reperfusion injury (IRI) and autoimmune diseases. This review summarizes the immunosuppressive actions of A2AR agonists in murine IRI models of liver, kidney, heart, lung and CNS, and gives details on the cellular effects of A2AR activation in neutrophils, macrophages, dendritic cells, natural killer cells, NKT cells, T effector cells and CD4+CD25+FoxP3+ T regulatory cells. This is discussed in the context of cytokine mediators involved in inflammatory cascades. Whilst the role of adenosine receptor agonists in various models of autoimmune disease has been well-documented, very little information is available regarding the role of A2AR activation in type 1 diabetes mellitus (T1DM). An overview of the pathogenesis of T1DM as well as early islet graft rejection in the immediate peri-transplantation period offers insight regarding the use of A2AR agonists as a beneficial intervention in clinical islet transplantation, promoting islet graft survival, minimizing early islet loss and reducing the number of islets required for successful transplantation, thereby increasing the availability of this procedure to a greater number of recipients. In summary, the use of A2AR agonists as a clinical intervention in IRI and as an adjunct to clinical immunesuppressive regimen in islet transplantation is highlighted.

show abstract

Section: Pathogenesis Of Type 1 Diabetes Mellitusmentioning

confidence: 99%

The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation

Chhabra¹,

Linden²,

Lobo³

et al. 2012

CDR

View full text Add to dashboard Cite

show abstract

“…These results are consistent with the idea that different iNKT-cell subpopulations have distinct functions and those expressing CD4 preferentially promote tolerance and conversely the DN subset contributes to anti-tumor activity and autoimmune pathogenicity 33–35 . It has also been shown that CD4 + iNKT cells suppressed T1D whereas the DN subset promoted diabetes development in NOD mice 36, 37 .…”

Section: Introductionmentioning

confidence: 97%

Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions

et al. 2013

View full text Add to dashboard Cite

Reduced frequency of invariant natural killer T (iNKT)-cells has been indicated as a contributing factor to type 1 diabetes (T1D) development in NOD mice. To further understand the genetic basis of the defect, we generated (NOD X ICR)F2 mice to map genes that control iNKT-cell development. We determined frequencies of thymic and splenic iNKT-cells as well as the ratio of CD4-positive and -negative subsets in the spleens of 209 F2 males. Quantitative trait loci (QTL) analysis revealed 5 loci that exceed the significant threshold for the frequency of thymic and/or splenic iNKT-cells on Chromosomes (Chr) 1, 5, 6, 12, and 17. Three significant loci on Chr 1, 4, and 5 were found for the ratio of CD4-positive and -negative splenic iNKT-cells. Comparisons to previously known mouse T1D susceptibility (Idd) loci revealed two significant QTL peak locations respectively mapped to Idd regions on Chr 4 and 6. The peak marker location of the significant Chr 12 iNKT QTL maps to within 0.5Mb of a syntenic human T1D locus. Collectively, our results reveal several novel loci controlling iNKT-cell development and provide additional information for future T1D genetic studies.

show abstract

“…In addition, it has been reported that NKT17 could play a pathogenic role in the pathophysiology of diabetes[41]. Therefore, we speculate that studies addressing the roles of SDC-1 expressing NKT17 cell may provide an alternative approach to understanding its role in fat metabolism and glucose homeostasis.…”

Section: Introductionmentioning

confidence: 89%

“…IL-17 is a potent proinflammatory cytokines that is required in host defense against infections[39] and been implicated in pathogenesis of asthma[40], and autoimmune diseases such as type 1 diabetes[41-43] and regulation of body fat[44]. In addition, IL-17 has been reported to modulate both adipogenesis and functions of adipocytes and glucose metabolism in mice[44,45].…”

Section: Introductionmentioning

confidence: 99%

Syndecan-1-coating of interleukin-17-producing natural killer T cells provides a specific method for their visualization and analysis

Jaiswal

Sadasivam

Hamad

2017

WJD

View full text Add to dashboard Cite

Natural killer T cells (NKT cells) are innate-like T cells that acquire effector functions while developing in the thymus, polarize into three distinct functional subsets viz. NKT1, NKT2 and NKT17 cells that produce interferon (IFN)-γ, interleukin (IL)-4 and IL-17, respectively. However, there has been no unique surface markers that define each subsets, forcing investigators to use intracellular staining of transcription factors and cytokines in combination of surface markers to distinguish among these subsets. Intracellular staining, however, causes apoptosis and prevents subsequent utilization of NKT cells in functional in vitro and in vivo assays that require viable cells. This limitation has significantly impeded understanding the specific properties of each subset and their interactions with each other. Therefore, there has been fervent efforts to find a specific markers for each NKT cell subset. We have recently identified that syndecan-1 (SDC-1; CD138) as a specific surface marker of NKT17 cells. This discovery now allows visualization of NKT17 in situ and study of their peripheral tissue distribution, characteristics of their TCR and viable sorting for in vitro and in vivo analysis. In addition, it lays the ground working for investigating significance of SDC-1 expression on this particular subset in regulating their roles in host defense and glucose metabolism.

show abstract

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

Cited by 42 publications

References 53 publications

The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation

The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation

Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions

Syndecan-1-coating of interleukin-17-producing natural killer T cells provides a specific method for their visualization and analysis

Contact Info

Product

Resources

About