Emerging concepts on inhibitors of indoleamine 2,3-dioxygenase in rheumatic diseases

P. Filippini, Paolo Nicola Filippini, N. Del Papa, D. Sambataro, A. Del Bufalo, Franco Locatelli, S. Rutella

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is now emerging. In particular, IDO1 can either support or antagonize inflammation in a context-and tissue-dependent manner. Studies in experimental arthritis have unravelled a previously unappreciated role for IDO in controlling B-cell activation and autoantibody production. IDO dysregulation has been documented in patients with systemic lupus erythematosus, systemic sclerosis and Sjogren's syndrome, as well as in severe sepsis and chronic kidney disease. This article summarizes the contribution of IDO to the pathophysiology of inflammatory/autoimmune disorders, and discusses whether strategies to restore metabolic equilibrium in the kynurenine pathway might be pursued in diseases states such as rheumatoid arthritis and systemic sclerosis.
Lingua originaleEnglish
pagine (da-a)5381-5393
Numero di pagine13
RivistaCurrent Medicinal Chemistry
Volume19
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Autoimmunity
  • dendritic cell
  • indoleamine 2,3-dioxygenase
  • interferon-gamma
  • rheumatoid arthritis
  • cancer
  • systemic lupus erythematosus
  • immune tolerance
  • regulatory T cell
  • hematopoietic growth factors
  • systemic sclerosis

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