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SLC7A5, known as large neutral amino acid transporter 1 (LAT-1), is a transporter dedicated to the transport of essential amino acids ( 21). T-cell receptor (TCR) stimulation triggers dramatic metabolic changes including increased glycolysis, pentose phosphate pathway activity, and glutaminolysis ( 19, 20). Amino Acid TransportersĪmino acid transporters are important in transporting amino acids from the environment into the cell ( 19). Here we summarize amino acid metabolism in mice and people with SLE with a focus on T cells. The importance of glycolysis, and fatty acid oxidation/synthesis in lupus T cells has been extensively reviewed elsewhere ( 8– 10, 16– 18). It has been documented that some amino acids such as leucine, methionine, glutamine, arginine, and alanine, are more essential than other amino acids during T cell activation and expansion or in determining distinct T cell fates ( 14, 15). Furthermore, amino acids are also critical for the biosynthesis of nucleotides ( 13). Amino acid metabolism is used in many processes that are involved in cell proliferation, growth and cell function. Essential amino acids cannot be synthesized within the body and must be supplied through dietary intake. Amino acids are classified as essential (leucine, isoleucine, lysine, histidine, valine, threonine, phenylalanine, tryptophan, and methionine), conditionally essential (glutamine, arginine, cysteine, glycine, proline, and tyrosine), or non-essential (alanine, glutamate, serine, asparagine, and aspartate) ( 12). Cell metabolism operates mainly through glycolysis, fatty acid oxidation and amino acid metabolism including glutaminolysis ( 8– 11). Recent studies have shown that the differentiation and function of each T cell subset is controlled by intracellular metabolic processes ( 8– 10). Since helper T cells can activate B cells to secrete antibodies, which are also involved in the lupus pathogenesis, T cells have earned claim as main therapeutic targets in patients with SLE ( 7). Many subsets of T cells, especially Th1, Th17, regulatory T (Treg) cells, and double-negative (CD4 -CD8 -) T cells, are involved through distinct mechanisms in the development of organ inflammation in SLE ( 6). T cells have a vital role in the pathogenesis of SLE. These factors, acting serially or simultaneously, lead to generalize breakdown of tolerance to self-antigens, which results in autoantibody production and tissue inflammation ( 5). The etiology of SLE is multifactorial and includes contributions from genetic, environmental, hormonal and epigenetic factors ( 2). SLE can affect practically all organs, including skin, kidney, and central nerve system ( 2– 4). Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibody production, immune complex deposition, tissue inflammation and damage of multiple organs ( 1). New insights in amino acid handling by T cells should guide approaches to correct T cell abnormalities and disease pathology. Here, we review the mechanisms whereby amino acid transport and metabolism affects T cell activation, differentiation and function in T cells in the prototype systemic autoimmune disease systemic lupus erythematosus. It appears that each T cell subset favors a unique metabolic process and that metabolic reprogramming changes cell fate. Besides glycolysis and fatty acid oxidation/synthesis, amino acid metabolism is also crucial in T cell metabolism. T cell metabolism is central to cell proliferation, survival, differentiation, and aberrations have been linked to the pathophysiology of systemic autoimmune diseases. 2Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.1Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.Michihito Kono 1*†, Nobuya Yoshida 2*† and George C.