Amino acid catabolism

A pivotal regulator of innate and adaptive immunity

Tracy L. Mcgaha, Lei Huang, Henrique Lemos, Richard Metz, Mario Mautino, George C. Prendergast, Andrew L. Mellor

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)135-157
Number of pages23
JournalImmunological Reviews
Volume249
Issue number1
DOIs
StatePublished - Sep 1 2012

Fingerprint

Adaptive Immunity
Innate Immunity
Amino Acids
Immunity
Antigen-Presenting Cells
Autoimmunity
Tryptophan
Cues
Cell Survival
Carcinogenesis
Homeostasis
Lymphocytes
Inflammation
Gene Expression
Pregnancy

Keywords

  • AHR
  • D-1MT
  • IDO
  • eif2ak4
  • mTOR
  • tolerance

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Mcgaha, T. L., Huang, L., Lemos, H., Metz, R., Mautino, M., Prendergast, G. C., & Mellor, A. L. (2012). Amino acid catabolism: A pivotal regulator of innate and adaptive immunity. Immunological Reviews, 249(1), 135-157. https://doi.org/10.1111/j.1600-065X.2012.01149.x

Amino acid catabolism : A pivotal regulator of innate and adaptive immunity. / Mcgaha, Tracy L.; Huang, Lei; Lemos, Henrique; Metz, Richard; Mautino, Mario; Prendergast, George C.; Mellor, Andrew L.

In: Immunological Reviews, Vol. 249, No. 1, 01.09.2012, p. 135-157.

Research output: Contribution to journalArticle

Mcgaha, TL, Huang, L, Lemos, H, Metz, R, Mautino, M, Prendergast, GC & Mellor, AL 2012, 'Amino acid catabolism: A pivotal regulator of innate and adaptive immunity', Immunological Reviews, vol. 249, no. 1, pp. 135-157. https://doi.org/10.1111/j.1600-065X.2012.01149.x
Mcgaha TL, Huang L, Lemos H, Metz R, Mautino M, Prendergast GC et al. Amino acid catabolism: A pivotal regulator of innate and adaptive immunity. Immunological Reviews. 2012 Sep 1;249(1):135-157. https://doi.org/10.1111/j.1600-065X.2012.01149.x
Mcgaha, Tracy L. ; Huang, Lei ; Lemos, Henrique ; Metz, Richard ; Mautino, Mario ; Prendergast, George C. ; Mellor, Andrew L. / Amino acid catabolism : A pivotal regulator of innate and adaptive immunity. In: Immunological Reviews. 2012 ; Vol. 249, No. 1. pp. 135-157.
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