2019
DOI: 10.3390/ijms20071676
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Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice

Abstract: Antigen-presenting cells (APCs) including dendritic cells (DCs) play a critical role in the development of autoimmune diseases by presenting self-antigen to T-cells. Different signals modulate the ability of APCs to activate or tolerize autoreactive T-cells. Since the expression of heme oxygenase-1 (HO-1) by APCs has been associated with the tolerization of autoreactive T-cells, we hypothesized that HO-1 expression might be altered in APCs from autoimmune-prone non-obese diabetic (NOD) mice. We found that, com… Show more

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Cited by 8 publications
(8 citation statements)
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“…Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the presence of islet autoantibodies and autoreactive T cells, pancreatic beta cell loss, and hyperglycemia (Figure 3) (248). Up-regulation of HO-1 in DCs prevented the increase in glycemia in non-obese diabetic (NOD) mice and a lower T1D incidence, suggesting it as a potential therapeutic approach for T1D treatment (249). Furthermore, a short-term induction of HO-1 promotes the recruitment of mesenchymal cells, M2 macrophages, and fibrocytes with repair properties, preventing T1D development in rats (250).…”
Section: Type 1 Diabetesmentioning
confidence: 99%
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“…Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the presence of islet autoantibodies and autoreactive T cells, pancreatic beta cell loss, and hyperglycemia (Figure 3) (248). Up-regulation of HO-1 in DCs prevented the increase in glycemia in non-obese diabetic (NOD) mice and a lower T1D incidence, suggesting it as a potential therapeutic approach for T1D treatment (249). Furthermore, a short-term induction of HO-1 promotes the recruitment of mesenchymal cells, M2 macrophages, and fibrocytes with repair properties, preventing T1D development in rats (250).…”
Section: Type 1 Diabetesmentioning
confidence: 99%
“…Furthermore, a short-term induction of HO-1 promotes the recruitment of mesenchymal cells, M2 macrophages, and fibrocytes with repair properties, preventing T1D development in rats (250). Interestingly, genetic restoration of HO-1 expression in DCs from NOD mice reduces T1D incidence highlighting their role in tolerizing autoreactive T-cells (249). It has been shown that resveratrol administration in drinking water attenuates biochemical changes associated with diabetes, and this protective role is mediated by TGF-β reduction and HO-1 induction (235).…”
Section: Type 1 Diabetesmentioning
confidence: 99%
“…Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is considered the key transcription factor responsible for controlling the activity of key antioxidant factors including heme oxygenase-1 (HO-1) [ 9 ]. Nrf2 pathway activation occurs under stressful conditions and is essential for sensing oxidative stress and in protecting cells against ROS [ 10 ]. Nrf2 has been reported to play protective roles in myocardial ischemia and reperfusion injury [ 11 ], sepsis [ 12 ], and neurodegenerative diseases [ 13 ].…”
Section: Introductionmentioning
confidence: 99%
“…A recent study highlights that NOD mice, a common murine model for diabetes, exhibit lower amount of dendritic cell (DC) expressing HO-1. This type of APC is responsible of autoreactive T-cell activation in T1DM [121]. Interestingly, the authors observed how the restoration of HO-1 expression reduced the incidence of T1DM [121].…”
Section: Diabetesmentioning
confidence: 99%