Interleukin-17 (IL-17) producing helper T (Th) 17 cells play a critical role in inflammatory autoimmune diseases which are caused by autoreactive cells that respond to self-antigens. The interaction between autoreactive T cells and effector cells, such as neutrophils and macrophages generates inflam...
Interleukin-17 (IL-17) producing helper T (Th) 17 cells play a critical role in inflammatory autoimmune diseases which are caused by autoreactive cells that respond to self-antigens. The interaction between autoreactive T cells and effector cells, such as neutrophils and macrophages generates inflammatory environment in autoimmune disease, including high level of reactive oxygen species (ROS) that induces oxidative stress. Therefore, I thought that ROS-inducible factors are crucial in control of autoimmune diseases. Since it has been reported that nuclear factor erythroid 2-related factor 2 (Nrf2) known as one of key antioxidant transcription factors also regulates CD4 T cell differentiation, I hypothesized that Nrf2 would be involved in progress of autoimmune diseases by regulation of Th17 cell differentiation. First, to test how Nrf2 regulates the differentiation and function of Th17 cells, I used Nrf2 deficient (KO) or overexpressing (Tg) mouse models. I found that Th17 cell differentiation was significantly enhanced in Nrf2KO mice, whereas inhibited in Nrf2Tg mice. In order to confirm the role of Nrf2 in autoimmune disease, I induced experimental autoimmune encephalomyelitis (EAE), an animal model of Th17 cell-mediated multiple sclerosis (MS), in wild type (WT), Nrf2KO, and Nrf2Tg mice. Strikingly, EAE disease progression in Nrf2Tg mice was markedly reduced compared to WT and NrfKO mice, with delayed disease onset and lower clinical scores. In contrast, the Nrf2KO mice showed increased the severity of inflammatory autoimmune disease. Moreover, I found that the Nrf2KO mice showed increased numbers of spinal-cord-infiltrating CD4+ T cells, which correlated with increased percentages and numbers of Th1 and Th17 cells and IL-17, IFNγ double-producing CD4+ T cells. Reversely, these cells frequency slightly decreased in Nrf2Tg mice. These data suggest that the Nrf2 is a critical player for regulation of Th 17 cell differentiation and autoimmune neuron diseases.
Interleukin-17 (IL-17) producing helper T (Th) 17 cells play a critical role in inflammatory autoimmune diseases which are caused by autoreactive cells that respond to self-antigens. The interaction between autoreactive T cells and effector cells, such as neutrophils and macrophages generates inflammatory environment in autoimmune disease, including high level of reactive oxygen species (ROS) that induces oxidative stress. Therefore, I thought that ROS-inducible factors are crucial in control of autoimmune diseases. Since it has been reported that nuclear factor erythroid 2-related factor 2 (Nrf2) known as one of key antioxidant transcription factors also regulates CD4 T cell differentiation, I hypothesized that Nrf2 would be involved in progress of autoimmune diseases by regulation of Th17 cell differentiation. First, to test how Nrf2 regulates the differentiation and function of Th17 cells, I used Nrf2 deficient (KO) or overexpressing (Tg) mouse models. I found that Th17 cell differentiation was significantly enhanced in Nrf2KO mice, whereas inhibited in Nrf2Tg mice. In order to confirm the role of Nrf2 in autoimmune disease, I induced experimental autoimmune encephalomyelitis (EAE), an animal model of Th17 cell-mediated multiple sclerosis (MS), in wild type (WT), Nrf2KO, and Nrf2Tg mice. Strikingly, EAE disease progression in Nrf2Tg mice was markedly reduced compared to WT and NrfKO mice, with delayed disease onset and lower clinical scores. In contrast, the Nrf2KO mice showed increased the severity of inflammatory autoimmune disease. Moreover, I found that the Nrf2KO mice showed increased numbers of spinal-cord-infiltrating CD4+ T cells, which correlated with increased percentages and numbers of Th1 and Th17 cells and IL-17, IFNγ double-producing CD4+ T cells. Reversely, these cells frequency slightly decreased in Nrf2Tg mice. These data suggest that the Nrf2 is a critical player for regulation of Th 17 cell differentiation and autoimmune neuron diseases.
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