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Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

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 meta...

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Autores principales: Panfili, Eleonora, Gerli, Roberto, Grohmann, Ursula, Pallotta, Maria Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563518/
https://www.ncbi.nlm.nih.gov/pubmed/32899743
http://dx.doi.org/10.3390/biom10091280
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author Panfili, Eleonora
Gerli, Roberto
Grohmann, Ursula
Pallotta, Maria Teresa
author_facet Panfili, Eleonora
Gerli, Roberto
Grohmann, Ursula
Pallotta, Maria Teresa
author_sort Panfili, Eleonora
collection PubMed
description 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.
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spelling pubmed-75635182020-10-27 Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe? Panfili, Eleonora Gerli, Roberto Grohmann, Ursula Pallotta, Maria Teresa Biomolecules Review 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. MDPI 2020-09-04 /pmc/articles/PMC7563518/ /pubmed/32899743 http://dx.doi.org/10.3390/biom10091280 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Panfili, Eleonora
Gerli, Roberto
Grohmann, Ursula
Pallotta, Maria Teresa
Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?
title Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?
title_full Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?
title_fullStr Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?
title_full_unstemmed Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?
title_short Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?
title_sort amino acid metabolism in rheumatoid arthritis: friend or foe?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563518/
https://www.ncbi.nlm.nih.gov/pubmed/32899743
http://dx.doi.org/10.3390/biom10091280
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