Arginine-dependent immune responses

• Published in: Cellular and molecular life sciences : CMLS Vol. 78; no. 13; pp. 5303 - 5324
• Main Authors: Martí i Líndez, Adrià-Arnau, Reith, Walter
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.07.2021; Springer Nature B.V
• Subjects: Amino acids; Arginine; Autoimmune diseases; Autoimmunity; Availability; Biochemistry; Biomedical and Life Sciences; Biomedicine; biosynthesis; Catabolism; Cell Biology; Dendritic cells; Divergence; evolution; Immune response; Immune system; Immunomodulation; Infectious diseases; Inflammation; Life Sciences; Lymphocytes; Lymphocytes T; Macrophages; Metabolic pathways; Metabolism; Modulators; Protein biosynthesis; Protein synthesis; Review; Substrates; T-lymphocytes; Immunometabolism; Arginase 1; Arginase 2; NOS; Arginine metabolism; Nitric oxide synthase; Arginase; Immunity
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-021-03828-4

A growing body of evidence indicates that, over the course of evolution of the immune system, arginine has been selected as a node for the regulation of immune responses. An appropriate supply of arginine has long been associated with the improvement of immune responses. In addition to being a building block for protein synthesis, arginine serves as a substrate for distinct metabolic pathways that profoundly affect immune cell biology; especially macrophage, dendritic cell and T cell immunobiology. Arginine availability, synthesis, and catabolism are highly interrelated aspects of immune responses and their fine-tuning can dictate divergent pro-inflammatory or anti-inflammatory immune outcomes. Here, we review the organismal pathways of arginine metabolism in humans and rodents, as essential modulators of the availability of this semi-essential amino acid for immune cells. We subsequently review well-established and novel findings on the functional impact of arginine biosynthetic and catabolic pathways on the main immune cell lineages. Finally, as arginine has emerged as a molecule impacting on a plethora of immune functions, we integrate key notions on how the disruption or perversion of arginine metabolism is implicated in pathologies ranging from infectious diseases to autoimmunity and cancer.