Analysis Tools
immune system
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• mice show increased susceptibility to dextran sodium sulfate (DSS)-induced acute colitis, showing rapid body weight loss, increased clinical scores, exacerbated colon length shortening, increased inflammatory cells into the colon
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• mice show elevated IFN-gamma-producing CD8+ effector T cell proportions in the spleen and mesenteric lymph nodes at 10 weeks of age
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• mice show low regulatory T (T reg) cell percentages in the spleen and mesenteric lymph nodes at 10 months of age
• however, T cell development and peripheral T cell homeostasis is not affected and T reg cell percentages in the thymus, spleen, and peripheral lymph nodes are normal in 6-week-old mice
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• adoptive transfer of mutant T reg cells with naive CD45RBhiCD4+ T cells into RAG-1 deficient mice results in gradual weight loss and a greater frequency of IFN-gamma-producing effector CD4+ T cells that is not seen with wild-type T reg cells
• the fraction of FoxP3+ cells from mice transferred with mutant T reg cells and naive CD45RBhiCD4+ T cells is decreased compared with those from mice transferred with wild-type T reg cells
• mutant T reg cells transferred into RAG-1 deficient mice cause gradual weight loss, show a more profound loss of Foxp3 expression, and the FoxP3-mainting fraction of mutant T reg cells produce higher amounts of IFN-gamma
• T reg cells exhibit higher baseline and maximum glycolytic rates (increased extracellular acidification rate), indicating hyperglycolysis, however baseline and maximum OXPHOS rates (increased mitochondrial oxygen consumption rate) are not affected
• T regs treated with dichloroacetic acid, which shifts glycolysis towards OXPHOS, show diminished IFN-gamma production
• treatment of stimulated T reg cells with the mTORC1 inhibitor rapamycin lowers the extracellular acidification rate and diminishes IFN-gamma production
• autophagy levels are decreased in T reg cells and autophagy induction after TCR stimulation is severely, but not completely, blocked in T reg cells
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• mice exhibit severe autoimmune symptoms with lymphocytic infiltration in many nonlymphoid organs at 10 months of age
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digestive/alimentary system
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• mice show increased susceptibility to dextran sodium sulfate (DSS)-induced acute colitis, showing rapid body weight loss, increased clinical scores, exacerbated colon length shortening, increased inflammatory cells into the colon
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hematopoietic system
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• mice show elevated IFN-gamma-producing CD8+ effector T cell proportions in the spleen and mesenteric lymph nodes at 10 weeks of age
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• mice show low regulatory T (T reg) cell percentages in the spleen and mesenteric lymph nodes at 10 months of age
• however, T cell development and peripheral T cell homeostasis is not affected and T reg cell percentages in the thymus, spleen, and peripheral lymph nodes are normal in 6-week-old mice
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• adoptive transfer of mutant T reg cells with naive CD45RBhiCD4+ T cells into RAG-1 deficient mice results in gradual weight loss and a greater frequency of IFN-gamma-producing effector CD4+ T cells that is not seen with wild-type T reg cells
• the fraction of FoxP3+ cells from mice transferred with mutant T reg cells and naive CD45RBhiCD4+ T cells is decreased compared with those from mice transferred with wild-type T reg cells
• mutant T reg cells transferred into RAG-1 deficient mice cause gradual weight loss, show a more profound loss of Foxp3 expression, and the FoxP3-mainting fraction of mutant T reg cells produce higher amounts of IFN-gamma
• T reg cells exhibit higher baseline and maximum glycolytic rates (increased extracellular acidification rate), indicating hyperglycolysis, however baseline and maximum OXPHOS rates (increased mitochondrial oxygen consumption rate) are not affected
• T regs treated with dichloroacetic acid, which shifts glycolysis towards OXPHOS, show diminished IFN-gamma production
• treatment of stimulated T reg cells with the mTORC1 inhibitor rapamycin lowers the extracellular acidification rate and diminishes IFN-gamma production
• autophagy levels are decreased in T reg cells and autophagy induction after TCR stimulation is severely, but not completely, blocked in T reg cells
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homeostasis/metabolism
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• mice show increased susceptibility to azoxymethane and DSS-induced colitis-associated cancer, showing higher tumor numbers in the colon than wild-type mice
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neoplasm
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• mice show increased susceptibility to azoxymethane and DSS-induced colitis-associated cancer, showing higher tumor numbers in the colon than wild-type mice
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