In experiments involving mice, increasing dietary arginine reduced the formation of colon cancer tumors and lessened the severity of influenza and SARS-CoV-2 infections:
Remarkably, providing arginine after mice had already contracted influenza also improved their outcomes.
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In 2023, the researchers discovered that depriving colon cancer cells of arginine caused them to accumulate more genetic mutations. These changes can contribute to the unpredictable behavior of cancer cells, raising important questions about how arginine shortages might influence the disease.
The latest study reveals another potentially significant consequence. When arginine becomes scarce, cells struggle to produce enough of a crucial immune system protein known as MHC-1. This protein acts as a warning system, helping immune cells identify potential dangers such as cancerous changes or viral infections.
Without enough MHC-1, abnormal or infected cells may become harder for the immune system to recognize.
Encouragingly, the researchers also found that supplying a moderate amount of arginine, comparable to the quantity available in a couple of over-the-counter supplement tablets, could help restore production of this important protein.
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“One of the most dramatic patterns to emerge was that arginine was the most depleted amino acid in all of these diseases,” she says.
In laboratory experiments using cultured cells, Wu examined how arginine shortages affected protein production. She identified 414 proteins whose levels dropped abnormally when arginine was scarce.
Many of these proteins were associated with biological functions already known to depend on arginine. However, the researchers uncovered a more unexpected effect involving three genes from the HLA family.
These genes provide instructions for producing proteins associated with MHC-I (major histocompatibility complex class I), an essential component of the immune system’s ability to recognize threats.
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When arginine was unavailable, ribosomes stalled while trying to manufacture MHC-I proteins. Without enough of the required amino acid, the cells could not efficiently complete the process.
As a result, fewer MHC-I proteins reached the cell surface, reducing the signals that would normally alert T cells to cancer-associated or viral proteins. This created an opportunity for dangerous cells to avoid immune detection.