Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Metabolism Année : 2015

Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production

Sarvenaz Metghalchi
  • Fonction : Auteur
Padmapriya Ponnuswamy
  • Fonction : Auteur
Yacine Haddad
  • Fonction : Auteur
  • PersonId : 969588
Ludivine Laurans
  • Fonction : Auteur
Marion Dalloz
  • Fonction : Auteur
Melissa Romain
  • Fonction : Auteur
Vincent Koropoulis
  • Fonction : Auteur
Salma Kotti
  • Fonction : Auteur
  • PersonId : 950800
Hester Den Ruijter
  • Fonction : Auteur
Alain Tedgui
  • Fonction : Auteur
  • PersonId : 929948

Résumé

Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme that catalizes the degradation of tryptophan along the kynurenine pathway. Here, we show that Ido1 activity sustains an immunostimulatory potential through inhibition of interleukin (Il)10. In atherosclerosis, Ido1-dependent inhibition of Il10 translates into disease exacerbation. The resistance of Ido1-deficient mice to enhanced immune activation is broken in Ido1/Il10 double-deficient mice, which show exaggerated immune responses and develop severe spontaneous colitis. We demonstrate that Ido1 activity is required for the regulation of Il10 and that kynurenic acid (Kna), an Ido1-derived metabolite, is responsible for reduced Il10 production through activation of a cAMP-dependent pathway and inhibition of Erk1/2 phosphorylation. Resupplementation of Ido1-deficient mice with Kna limits Il10 expression and promotes atherosclerosis. In human atherosclerotic lesions, increased levels of Kna are associated with an unstable plaque phenotype, and its blood levels predict death and recurrent myocardial infarction in patients with coronary artery disease.

Dates et versions

hal-01376843 , version 1 (05-10-2016)

Identifiants

Citer

Sarvenaz Metghalchi, Padmapriya Ponnuswamy, Tabassome Simon, Yacine Haddad, Ludivine Laurans, et al.. Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production. Cell Metabolism, 2015, 22 (3), pp.460-471. ⟨10.1016/j.cmet.2015.07.004⟩. ⟨hal-01376843⟩
577 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More