Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?
Eleonora PanfiliRoberto GerliUrsula GrohmannMaria Teresa PallottaPublished in: Biomolecules (2020)
In mammals, amino acid metabolism has evolved to act as a critical regulator of innate and adaptive immune responses. Rheumatoid arthritis (RA) is the most common form of inflammatory arthropathy sustained by autoimmune responses. We examine here the current knowledge of tryptophan and arginine metabolisms and the main immunoregulatory pathways in amino acid catabolism, in both RA patients and experimental models of arthritis. We found that l-tryptophan (Trp) metabolism and, in particular, the kynurenine pathway would exert protective effects in all experimental models and in some, but not all, RA patients, possibly due to single nucleotide polymorphisms in the gene coding for indoleamine 2,3-dioxygenase 1 (IDO1; the enzyme catalyzing the rate-limiting step of the kynurenine pathway). The function, i.e., either protective or pathogenetic, of the l-arginine (Arg) metabolism in RA was less clear. In fact, although immunoregulatory arginase 1 (ARG1) was highly induced at the synovial level in RA patients, its true functional role is still unknown, possibly because of few available preclinical data. Therefore, our analysis would indicate that amino acid metabolism represents a fruitful area of research for new drug targets for a more effective and safe therapy of RA and that further studies are demanding to pursue such an important objective.
Keyphrases
- rheumatoid arthritis
- amino acid
- end stage renal disease
- disease activity
- immune response
- ejection fraction
- newly diagnosed
- chronic kidney disease
- healthcare
- nitric oxide
- prognostic factors
- peritoneal dialysis
- emergency department
- systemic lupus erythematosus
- gene expression
- stem cells
- machine learning
- patient reported outcomes
- toll like receptor
- idiopathic pulmonary fibrosis
- patient reported
- electronic health record
- drug induced
- nitric oxide synthase
- copy number
- big data