This article is reproduced from the "China Biotechnology Network" public account.
Within mammalian cells, magnesium (Mg) is one of the most important micronutrients, and hundreds of enzymes require magnesium ions as essential cofactors. Magnesium is involved in more than 300 chemical reactions in the human body. It not only helps muscles contract, assists nerves in sending and receiving messages, but also assists the heart in beating steadily. In addition, magnesium also makes our immune system stronger. Most people can supplement magnesium with foods such as green leafy vegetables, whole grains, and legumes.
Over the past two decades, the role of magnesium in organisms has been extensively studied, especially the link between magnesium levels in the blood (serum magnesium) and the immune system. Serum magnesium levels are an important factor in the immune system's ability to fight off pathogens and cancer cells. Therefore, magnesium deficiency has been linked to a variety of diseases, including infections and cancer. To date, however, little is known to scientists about how magnesium affects the immune system.
In the early morning of January 20, Beijing time, a new study published in Cell found that T cells can only effectively eliminate abnormal or infected cells in a magnesium-rich environment, so that the immune system can work effectively. This finding will have important implications for cancer treatment.
Research Results (Source: Cell)
Previous studies have found that low dietary magnesium intake and hypomagnesemia are associated with pathophysiology of various diseases, including infections and cancer. Studies have shown that in mice fed a diet lacking magnesium, the metastatic spread of cancer cells accelerates, and the animals' defense against influenza viruses is also affected due to insufficient induced T cell kinase (ITK) activity.
In these models, whether extracellular magnesium contributes to the formation of an adaptive immune response has not been evaluated. CD8+ T cells are an important part of the adaptive immune system and play an important role in recognizing and clearing infected or malignantly transformed cells.
In the new study, the researchers found that CD8+ T cells were only effective in eliminating abnormal or infected cells in a magnesium-rich environment. Magnesium is essential for a T cell surface protein called LFA-1, which plays a key role in T cell activation.
Specifically, co-stimulation of cell surface molecule LFA-1 requires magnesium to employ its active conformation on CD8+ T cells, thereby increasing calcium flow, signal transduction, metabolic reprogramming, immune synapse formation, and enhanced T cytotoxicity.
T cells (blue) form immune synapses through LFA-1, attacking tumor cells (white)
The researchers explain that in an inactive state, LFA-1 is in a curved structure and therefore cannot effectively bind to infected or abnormal cells. This is where magnesium comes into play. If there is a high level of magnesium near the T cells, it binds to LFA-1 and ensures that it remains active.
The fact that magnesium is essential for the function of T cells may be a very important discovery in modern cancer immunotherapy. The purpose of these therapies is to mobilize the immune system, especially cytotoxic T cells, to fight cancer cells. In the experimental model, the researchers confirmed that the immune response of T cells to cancer cells is enhanced by an increase in local magnesium levels in the tumor.
By analyzing previous clinical data from cancer patients, the researchers demonstrated that immunotherapy was less effective in patients with insufficient serum magnesium levels.
Taken together, these findings conceptually link co-stimulation and nutrient perception and point to the "magnesium-LFA-1" axis as a therapeutic biological system.
Study corresponding author Professor Christoph Hess, from the Department of Biomedicine at the University of Basel, said: "Based on the available data, we are not yet able to answer the question of whether regular magnesium intake affects cancer risk. Next, we plan to conduct prospective studies to test the clinical effects of magnesium as a catalyst for the immune system. ”
Typography | Qiao Weijun
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Resources:
[1] Magnesium sensing via LFA-1 regulates CD8+ T cell effector function. Doi:org/10.1016/j.cell.2021.12.039