Challenging metabolism may help fight disease

Challenging metabolism may help fight disease

Researchers have published their findings in the journal Nature Communications looked at how immune system cells, which are essential to fighting infection and preventing diseases like cancer, use their metabolic pathways when they are activated in the laboratory.

When these infection and cancer fighting cells, known as CD4+ T cells, are challenged, they make enough energy to fuel their important cellular functions and to create biosynthetic building blocks to divide and increase to respond to challenges like an infection.

The researchers found that the cells do this by taking up nutrients and processing them through cellular metabolic pathways. When the cells are activated they re-programme their metabolic pathways in order to provide the energy and building blocks needed to carry out their function.

Dr Nick Jones, of Swansea University Medical School, who led the study said: "It is important to understand how these cells function metabolically as it might lead to new therapies to help treat infectious diseases and cancer. In this study we have scrutinised the metabolic pathways used by the immune cell and how a particular type of metabolism of the cells allows them to carry out these important functions. In doing so our results indicate that manipulating metabolism may have help to fight various diseases or disorders.

Authors show that at rest cultured human effector memory and central memory CD4+ T-cells have elevated levels of glycolysis and oxidative phosphorylation (OXPHOS), in comparison to naïve T-cells. Despite having low resting metabolic rates, naive T-cells respond to TCR stimulation with robust and rapid increases in glycolysis and OXPHOS.

This early metabolic switch requires Akt activity to support increased rates of glycolysis and STAT5 activity for amino acid biosynthesis and TCA cycle anaplerosis. Importantly, both STAT5 inhibition and disruption of TCA cycle anaplerosis are associated with reduced IL-2 production, demonstrating the functional importance of this early metabolic program.

These results define STAT5 as a key node in modulating the early metabolic program following activation in naive CD4+ T-cells and in turn provide greater understanding of how cellular metabolism shapes T-cell responses.

"Our next steps in our research will be understanding how differences in key sugars in our diet can affect the immune system response when challenged by bacteria" the author said.