Abstract
The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control the specificity, magnitude and persistence of the immune response. Numerous catabolic and anabolic processes are involved in this process, and prominent roles for l-arginine and l-glutamine catabolism have been described, as these amino acids serve as precursors of nitric oxide, creatine, agmatine, tricarboxylic acid cycle intermediates, nucleotides and other amino acids, as well as for ornithine, which is used to synthesize putrescine and the polyamines spermidine and spermine. Polyamines have several purported roles and high levels of polyamines are manifest in tumor cells as well in autoreactive B- and T-cells in autoimmune diseases. In the tumor microenvironment, l-arginine catabolism by both tumor cells and suppressive myeloid cells is known to dampen cytotoxic T-cell functions suggesting there might be links between polyamines and T-cell suppression. Here, we review studies suggesting roles of polyamines in normal immune cell function and highlight their connections to autoimmunity and anti-tumor immune cell function.
Highlights
Metabolic regulation is a vital component of a coordinated immune response [1].Dormant immune cells circulate in blood and tissues and morph into highly activated cells following antigen exposure
Given that ornithine decarboxylase (ODC) enzymatic activity is significantly increased after T-cell activation, polyamine production is an important part of normal T-cell function [82,92,93]
Inhibitor DFMO reduces pools of the methyl donor S-adenosylmethionine (SAM, an activated form of methionine) [160]. This appears to occur via effects of polyamines on harnessing the translation of SAM decarboxylase (SAMDC/AMD1) [161,162], which converts SAM to decarboxylated SAM
Summary
Metabolic regulation is a vital component of a coordinated immune response [1]. Dormant immune cells circulate in blood and tissues and morph into highly activated cells following antigen exposure. To achieve its diverse functions, the immune system is comprised of heterogeneous populations of cells that are each capable of a broad range of responses. All of these cells must adjust their metabolic activity to meet functional demands that include migration, proliferation and sometimes long-lasting persistence in these diverse environments [5,6]. A focused discussion is provided that reviews the roles of an understudied metabolic pathway in immune cells, that which controls polyamine homeostasis, in normal immune cell functions and immune-related diseases [9]
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