Altered transcriptional responses in the lungs of aged mice after influenza infection.

Background: Influenza causes a serious infection in older individuals who are at the highest risk for mortality from this virus. Changes in the immune system with age are well known. This study used transcriptomic analysis to evaluate how aging specifically affects the functional host response to influenza in the lung.

Glycolysis Inhibition Induces Functional and Metabolic Exhaustion of CD4 T Cells in Type 1 Diabetes.

In Type 1 Diabetes (T1D), CD4 T cells initiate autoimmune attack of pancreatic islet β cells. Importantly, bioenergetic programs dictate T cell function, with specific pathways required for progression through the T cell lifecycle. During activation, CD4 T cells undergo metabolic reprogramming to the less efficient aerobic glycolysis, similarly to highly proliferative cancer cells.

A Noncanonical Role for Plasminogen Activator Inhibitor Type 1 in Obesity-Induced Diabetes.

Obesity is a major risk factor for type 2 diabetes because of chronic hepatic inflammation and resultant insulin resistance. Hepatocyte growth factor (HGF) is responsible for resetting hepatic homeostasis after injury following activation by urokinase-type plasminogen activator (u-PA; encoded by the PLAU gene). Plasminogen activator inhibitor type-1 (PAI-1; encoded by the SERPINE1 gene), a u-PA inhibitor and antifibrinolytic agent, is often elevated in obesity and is linked to cardiovascular events.

Lymphocyte Activation Gene-3 Maintains Mitochondrial and Metabolic Quiescence in Naive CD4 T Cells.

Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed by CD4 T cells and tempers their homeostatic expansion. Because CD4 T cell proliferation is tightly coupled to bioenergetics, we investigate the role of LAG-3 in modulating naive CD4 T cell metabolism. LAG-3 deficiency enhances the metabolic profile of naive CD4 T cells by elevating levels of mitochondrial biogenesis.

Treatment with a Catalytic Superoxide Dismutase (SOD) Mimetic Improves Liver Steatosis, Insulin Sensitivity, and Inflammation in Obesity-Induced Type 2 Diabetes.

Oxidative stress and persistent inflammation are exaggerated through chronic over-nutrition and a sedentary lifestyle, resulting in insulin resistance. In type 2 diabetes (T2D), impaired insulin signaling leads to hyperglycemia and long-term complications, including metabolic liver dysfunction, resulting in non-alcoholic fatty liver disease (NAFLD). The manganese metalloporphyrin superoxide dismustase (SOD) mimetic, manganese (III) meso-tetrakis (-ethylpyridinium-2-yl) porphyrin (MnP), is an oxidoreductase known to scavenge reactive oxygen species (ROS) and decrease pro-inflammatory cytokine production, by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation.