Immune cells from patients with psoriasis are defective in inducing indoleamine 2,3-dioxygenase expression in response to inflammatory stimuli.
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.


OBJECTIVE
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.
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.|Dermatology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
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Llamas-Velasco
Centro de Biología Molecular 'Severo Ochoa', Universidad Autonoma de Madrid, Madrid, Spain.
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P
Bonay
Dermatology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
M
M
José Concha-Garzón
Centro de Biología Molecular 'Severo Ochoa', Universidad Autonoma de Madrid, Madrid, Spain.
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Corvo-Villén
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.|Immunology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
A
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Vara
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.|Immunology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
D
D
Cibrián
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.|Immunology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
A
A
Sanguino-Pascual
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.|Immunology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
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F
Sánchez-Madrid
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.|Immunology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
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H
de la Fuente
Instituto de Investigación Sanitaria Princesa, Madrid, Spain.|Dermatology Department, Instituto de Investigación Sanitaria Princesa, Diego de Leon 62, 28006, Madrid, Spain.
E
E
Daudén
D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000502:physiology; D004338:Drug Combinations; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007963:Leukocytes, Mononuclear; D008070:Lipopolysaccharides / Q000494:pharmacology; D011565:Psoriasis / Q000201:enzymology* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000502:physiology*
D016207:Cytokines; D004338:Drug Combinations; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides