Journal
NATURE IMMUNOLOGY
Volume 17, Issue 2, Pages 132-139Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3323
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Funding
- US National Institutes of Health
- Calithera Biosciences
- National Cancer Institute Cancer Core grant [P30 CA21765]
- American Lebanese Associated Charities
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Cells of the immune system are auxotrophs for most amino acids, including several nonessential ones. Arginine and tryptophan are used within the regulatory immune networks to control proliferation and function through pathways that actively deplete the amino acid from the microenvironment or that create regulatory molecules such as nitric oxide or kynurenines. How immune cells integrate information about essential amino acid supplies and then transfer these signals to growth and activation pathways remains unclear but has potential for pathway discovery about amino sensing. In applied research, strategies to harness amino acid auxotrophy so as to block cancerous lymphocyte growth have been attempted for decades with limited success. Emerging insights about amino acid metabolism may lead to new strategies in clinical medicine whereby both amino acid auxotrophy and the immunoregulatory pathways controlled by amino acids can be manipulated.
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