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Amino acid catabolism: a pivotal regulator of innate and adaptive immunity

Lookup NU author(s): Dr Lei HuangORCiD, Dr Henrique De Paula LemosORCiD, Emeritus Professor Andrew MellorORCiD


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Enhanced amino acid catabolism is a common response to inflammation, but the immunologic significance of altered amino acid consumption remains unclear. The finding that tryptophan catabolism helped maintain fetal tolerance during pregnancy provided novel insights into the significance of amino acid metabolism in controlling immunity. Recent advances in identifying molecular pathways that enhance amino acid catabolism and downstream mechanisms that affect immune cells in response to inflammatory cues support the notion that amino acid catabolism regulates innate and adaptive immune cells in pathologic settings. Cells expressing enzymes that degrade amino acids modulate antigen-presenting cell and lymphocyte functions and reveal critical roles for amino acid- and catabolite-sensing pathways in controlling gene expression, functions, and survival of immune cells. Basal amino acid catabolism may contribute to immune homeostasis that prevents autoimmunity, whereas elevated amino acid catalytic activity may reinforce immune suppression to promote tumorigenesis and persistence of some pathogens that cause chronic infections. For these reasons, there is considerable interest in generating novel drugs that inhibit or induce amino acid consumption and target downstream molecular pathways that control immunity. In this review, we summarize recent developments and highlight novel concepts and key outstanding questions in this active research field.

Publication metadata

Author(s): McGaha TL, Huang L, Lemos H, Metz R, Mautino M, Prendergast GC, Mellor AL

Publication type: Review

Publication status: Published

Journal: Immunological Reviews

Year: 2012

Volume: 249

Issue: 1

Pages: 135-157

Print publication date: 01/09/2012

ISSN (print): 0105-2896

ISSN (electronic): 1600-065X


DOI: 10.1111/j.1600-065X.2012.01149.x

PubMed id: 22889220