Immune Cells From Patients With Psoriasis Are Defective in Inducing Indoleamine 2,3-dioxygenase Expression in Response to Inflammatory Stimuli

Br J Dermatol. 2017 Mar;176(3):695-704. doi: 10.1111/bjd.14779. Epub 2016 Oct 17.

Abstract

Background: Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that suppresses the immune response. The role of IDO as a negative regulator of inflammatory responses has been documented in several experimental autoimmune diseases.

Objectives: To explore the regulation of IDO by immune cells in psoriasis and its relation with disease severity.

Methods: The expression and activity of IDO were assessed by reverse-transcriptase polymerase chain reaction, flow cytometry and high-performance liquid chromatography in peripheral blood of patients with moderate-to-severe plaque-type psoriasis. The ability of immune cells to express IDO in response to inflammatory stimuli was studied. The functional role of IDO expression was evaluated in a regulatory T cell (Treg) differentiation assay, using cocultures of immature monocyte-derived dendritic cells with autologous peripheral CD4+ T cells.

Results: Analysis of the kynurenine-to-tryptophan ratio in serum samples indicated higher IDO activity in patients with psoriasis than in healthy controls. However, correlation studies showed lower IDO activity in those patients with higher Psoriasis Area and Severity Index (PASI). Although myeloid dendritic cells from patients with psoriasis expressed higher levels of IDO than those from healthy controls, these cells did not upregulate IDO in response to a combination of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 cytokines. The defective expression of IDO correlated with PASI. Immature monocyte-derived dendritic cells from patients with psoriasis also expressed low levels of IDO and induced CD4+ Treg differentiation poorly.

Conclusions: Immune cells from patients with psoriasis have a defect in upregulating IDO in response to inflammation associated with the severity of psoriasis.

MeSH terms

  • Case-Control Studies
  • Cell Differentiation / immunology
  • Cytokines / pharmacology*
  • Dendritic Cells / physiology
  • Drug Combinations
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Leukocytes, Mononuclear
  • Lipopolysaccharides / pharmacology
  • Psoriasis / enzymology*
  • Psoriasis / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • Cytokines
  • Drug Combinations
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Lipopolysaccharides