New role for glucose in controlling immune responses!

New role for glucose in controlling immune responses!

Glucose - commonly referred to as a 'simple' sugar - may actually be crucial in the fight against cancer and inflammatory disease as scientists have just discovered a new role in which it stimulates cells that work on the front line in the fight against tumors and infection.

Glucose, which is generated from the food that we eat, is the most important fuel used in our bodies as our cells use it to generate energy and for growth and division. The cells of our immune system become very active during an immune response, such as when responding to infection, and as a result they tend to have high demands for glucose. Unsurprisingly, when immune cells are starved of glucose, as might occur within tumors for instance, they become dysfunctional.

However, new research shows that the immune cells that monitor our bodies for signs of danger (dendritic cells) are different -- when they are starved of glucose they actually become better at stimulating the vital players in the immune response (T lymphocytes).

Authors show a contrasting function for glucose in dendritic cells (DCs), as glucose represses the proinflammatory output of LPS-stimulated DCs and inhibits DC-induced T-cell responses. A glucose-sensitive signal transduction circuit involving the mTOR complex 1 (mTORC1), HIF1α and inducible nitric oxide synthase (iNOS) coordinates DC metabolism and function to limit DC-stimulated T-cell responses.

When multiple T cells interact with a DC, they compete for nutrients, which can limit glucose availability to the DCs. In such DCs, glucose-dependent signalling is inhibited, altering DC outputs and enhancing T-cell responses.

These data reveal a mechanism by which T cells regulate the DC microenvironment to control DC-induced T-cell responses and indicate that glucose is an important signal for shaping immune responses.

The scientists believe this opens the door to new therapeutic possibilities to regulate immune responses to cancers and other immune-related diseases.

Senior author said: "It is becoming clear that glucose is an important signaller in our immune system, in that cells that have access to glucose behave very differently to those that do not. We have discovered that dendritic cells are actually better at stimulating immune responses when starved of glucose, which is not the case for any of the other immune cells that have been analysed."

"The discovery that T cells and dendritic cells compete with each other for glucose offers a new and exciting insight into how glucose can regulate dendritic cell function. We hope that by better understanding how nutrients such as glucose control the immune response, we can go on to develop new therapies to tackle a host of debilitating immune-related diseases."