Amino acid catabolism: a pivotal regulator of innate and adaptive immunity.
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.
Immunotherapy Center, Georgia Health Sciences University, Augusta, GA 30912, USA. tmcgaha@georgiahealth.edu
Tracy L
TL
McGaha
Lei
L
Huang
Henrique
H
Lemos
Richard
R
Metz
Mario
M
Mautino
George C
GC
Prendergast
Andrew L
AL
Mellor
D056704:Adaptive Immunity; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017634:Self Tolerance; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000596:Amino Acids; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C546842:MTOR protein, human; C529271:EIF2AK4 protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases