Title:Emerging Concepts on Inhibitors of Indoleamine 2,3-Dioxygenase in Rheumatic Diseases
Volume: 19
Issue: 31
Author(s): P. Filippini, N. Del Papa, D. Sambataro, A. Del Bufalo, F. Locatelli and S. Rutella
Affiliation:
Keywords:
Autoimmunity, dendritic cell, indoleamine 2, 3-dioxygenase, interferon-γ, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, immune tolerance, regulatory T cell, hematopoietic growth factors, cancer
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 tissuedependent
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.