Aerobic Glycolysis Is Crucial to the Proper Functioning of NK Cells

Currently, a lot of research is being done to learn more about how natural killer (NK) cells, our allies in the fight against infection and cancer, work.

LDHA and NK Cell Function

LDHA and NK Cell Function. Image Courtesy of Cell Report

The Sloan Kettering Institute has conducted a study of natural killer (NK) lymphocytes, cells of the innate immune system, that function in a complex process. These natural killers specialize in detecting and responding to infections and they are the first to arrive on the scene of infection and limit the damage until reinforcement arrives. They have more than one trick up their sleeves: in addition to their rapid cytotoxicity, they are able to secrete cytokines and clone themselves.

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Cytokines are molecules of the immune system that act as messenger substances. They are secreted by lymphocytes and macrophages and act on other cells to regulate their activity.

To maintain this energy-intensive activity when called upon, NK cells must increase their metabolic activity. Since we still know little about this, the researchers investigated the role of aerobic glycolysis in vivo, since other immune cells, such as T cells, are known to depend on it. They found that after infection, the glycolytic rate of natural cytotoxic lymphocytes increases prior to that of CD8+ T cells. The deletion of lactate dehydrogenase A (LDHA an enzyme) revealed that the activated Natural Killer cells rely on this enzyme for both their function and their proliferation.  NK cells that are LDHA-deficient showed poor anti-viral and anti-tumor properties. In short, the study showed that aerobic glycolysis is very important to the proper functioning of NK cells.

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The importance of NK cells

The study of these cells is currently an important area of research in immunology. “There is currently a lot of interest in NK cells as a potential target for immunotherapy. The better we understand how they work, the better we can program them to fight disease,” says Joseph Sun, an immunologist at the Sloan Kettering Institute.

They could be used to treat patients with cancer and other diseases, through therapy, in which cells are grown in a laboratory and then introduced into the bloodstream. The process must be done in a controlled manner and not in a hurry to balance the rate of cell proliferation with the strength of the cells produced.

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Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function

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