Amino Acid Metabolism in Lupus

Abstract

T cell metabolism is central to cell proliferation, survival, differentiation, and aberrations have been linked to the pathophysiology of systemic autoimmune diseases. Besides glycolysis and fatty acid oxidation/synthesis, amino acid metabolism is also crucial in T cell metabolism. It appears that each T cell subset favors a unique metabolic process and that metabolic reprogramming changes cell fate. 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. New insights in amino acid handling by T cells should guide approaches to correct T cell abnormalities and disease pathology.

Keywords: T cell; amino acid; amino acid transporters; cell metabolism; systemic lupus erythematosus.

Figure 1

Amino acid transporters and metabolism in lupus T cells. Amino acid acquisition is crucial for cell function. Amino acid transporters play central roles in acquiring amino acids from the external environment. Some amino acids (e.g. leucine, methionine, glutamine, arginine, and alanine) are more essential than other amino acids in during T cell activation and expansion, or in determining different T cell fates in autoimmune diseases. Red arrows or letters indicate “enhance or active”, whereas blue arrows indicate “inhibit or inactivate”. ASCT2, alanine-serine-cysteine transporter 2; CaMK4, calcium/calmodulin–dependent protein kinase IV; CAT, cationic amino acid transporters; CREM, cAMP response element modulator; EAE, experimental autoimmune encephalomyelitis; ETC, electron transport chain; ICER, inducible cAMP early repressor; LAT-1, large neutral amino acid transporter 1; mTORC, mammalian target of rapamycin complex; OXPHOS, oxidative phosphorylation; PKM2, pyruvate kinase muscle isozyme 2; ROS, reactive oxygen species; SLE, systemic lupus erythematosus; TCA cycle, tricarboxylic acid cycle.