The role of AMPK in T cell metabolism and function.

The AMP-activated protein kinase (AMPK) is a key metabolic regulator that both senses changes in cellular energy levels and activates pathways to maintain cellular energy balance. AMPK achieves this by stimulating catabolic pathways that generate ATP and inhibiting biological pathways that consume ATP consumption. Recent work has established that AMPK is activated in T cells by both immunological and environmental stimuli, and plays an important role in T cell metabolism, in part by controlling T cell 'metabolic plasticity'.

The miR-17∼92 microRNA Cluster Is a Global Regulator of Tumor Metabolism.

A central hallmark of cancer cells is the reprogramming of cellular metabolism to meet the bioenergetic and biosynthetic demands of malignant growth. Here, we report that the miR-17∼92 microRNA (miRNA) cluster is an oncogenic driver of tumor metabolic reprogramming. Loss of miR-17∼92 in Myc(+) tumor cells leads to a global decrease in tumor cell metabolism, affecting both glycolytic and mitochondrial metabolism, whereas increased miR-17∼92 expression is sufficient to drive increased nutrient usage by tumor cells.

Amino acids fuel T cell-mediated inflammation.

Reprogramming cellular metabolism helps support T cell growth and effector function upon activation. In this issue of Immunity, Nakaya et al. (2014) report that the glutamine transporter ASCT2 regulates T cell metabolism and mTOR kinase signaling to shape inflammatory T helper cell responses.

Oxidative metabolism enables Salmonella evasion of the NLRP3 inflammasome.

Microbial infection triggers assembly of inflammasome complexes that promote caspase-1-dependent antimicrobial responses. Inflammasome assembly is mediated by members of the nucleotide binding domain leucine-rich repeat (NLR) protein family that respond to cytosolic bacterial products or disruption of cellular processes. Flagellin injected into host cells by invading Salmonella induces inflammasome activation through NLRC4, whereas NLRP3 is required for inflammasome activation in response to multiple stimuli, including microbial infection, tissue damage, and metabolic dysregulation, through mechanisms that remain poorly understood.

The AMP-activated protein kinase (AMPK) and cancer: many faces of a metabolic regulator.

The AMP-activated protein kinase (AMPK) is a central regulator of cellular metabolism and energy homeostasis in mammalian tissues. Pertinent to cancer biology is the fact that AMPK is situated in the center of a signaling network involving established tumor suppressors including LKB1, TSC2 and p53. However, recent research suggests that AMPK can exert pro- or anti-tumorigenic roles in cancer depending on context.

Fueling immunity: insights into metabolism and lymphocyte function.

Lymphocytes face major metabolic challenges upon activation. They must meet the bioenergetic and biosynthetic demands of increased cell proliferation and also adapt to changing environmental conditions, in which nutrients and oxygen may be limiting. An emerging theme in immunology is that metabolic reprogramming and lymphocyte activation are intricately linked.

Novel nonmajor histocompatibility complex-linked loci from mouse chromosome 17 confer susceptibility to viral-mediated chronic autoimmune myocarditis.

Background: Development of viral-induced chronic myocarditis is thought to involve both environmental and genetic factors. However, to date, no susceptibility genes have been identified.

Methods And Results: We sought to identify loci that confer susceptibility to viral-induced chronic myocarditis with the use of chromosome substitution strain mice that are composed of 1 chromosome from the disease susceptible A/J strain on an otherwise resistant C57BL/6 background.

IL-6 during viral-induced chronic autoimmune myocarditis.

Interleukin (IL)-6 is a pleiotropic cytokine that plays a key role in a wide variety of diseases. Based on a number of adjuvant-induced experimental models, IL-6 is critical to the development of autoimmune diseases including experimental autoimmune encephalomyelitis, adjuvant-induced arthritis, and experimental autoimmune myocarditis. However, whether it plays a pathogenic role in viral-induced autoimmune myocarditis has been less well defined.

Lack of IL-6 during coxsackievirus infection heightens the early immune response resulting in increased severity of chronic autoimmune myocarditis.

Background: Chronic myocarditis is often initiated by viral infection, the most common of which is coxsackievirus infection. The precise mechanism by which viral infection leads to chronic autoimmune pathology is poorly understood, however it is clear that the early immune response plays a critical role. Previous results have shown that the inflammatory cytokine interleukin (IL)-6 is integral to the development of experimental-induced autoimmune myocarditis.

Intestinal phenotype of variable-weight cystic fibrosis knockout mice.

Cystic fibrosis (CF) transmembrane conductance regulator (Cftr) knockout mice present the clinical features of low body weight and intestinal disease permitting an assessment of the interrelatedness of these phenotypes in a controlled environment. To identify intestinal alterations that are affected by body weight in CF mice, the histological phenotypes of crypt-villus axis height, goblet cell hyperplasia, mast cell infiltrate, crypt cell proliferation, and apoptosis were measured in a population of 12-wk-old (C57BL/6 x BALB/cJ) F2 Cftr(tm1UNC) and non-CF mice presenting a range of body weight. In addition, cardiac blood samples were assessed, and gene expression profiling of the ileum was completed.