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Amino acid auxotrophy as a system of immunological control nodes

Nature Immunology volume 17, pages 132–139 (2016)Cite this article

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Abstract

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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Figure 1: Regulated amino acid–metabolizing enzymes in immunity.
Figure 2: Arg1 in immune responses.
Figure 3: Arginine regeneration and the anaplerotic Krebs 'cycle' in M1 macrophages.
Figure 4: Clinical exploitation of amino acid auxotrophy.

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Acknowledgements

Research in the author's laboratory is supported by grants from the US National Institutes of Health, Calithera Biosciences, National Cancer Institute Cancer Core grant P30 CA21765 and the American Lebanese Associated Charities.

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  1. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Peter J Murray

  2. Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Peter J Murray

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The author's laboratory has a collaborative agreement with Calithera Biosciences to investigate aspects of arginine metabolism in immune responses. No personal funds are derived from this agreement.

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Murray, P. Amino acid auxotrophy as a system of immunological control nodes. Nat Immunol 17, 132–139 (2016). https://doi.org/10.1038/ni.3323

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