• Petri Niinisalo, Niku Oksala, Mari Levula, Markku Pelto-Huikko, Otso Järvinen, Juha-Pekka Salenius, Leena Kytömäki, Juhani T Soini, Mika Kähönen, Reijo Laaksonen, Mikko Hurme, and Terho Lehtimäki.
• Department of Clinical Chemistry, University of Tampere, Medical School, and Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland. petri.niinisalo@uta.fi
• Ann. Med. 2010 Jan 1; 42 (1): 55-63.

ObjectiveWe aimed to characterize the expression of indoleamine 2,3-dioxygenase (IDO) or IDO-induced tryptophan degradation-dependent pathways, which may lead to suppression of T cells and possible protection against atherosclerosis.Methods And ResultsExpression of IDO and IDO-related pathway components was analyzed in advanced human atherosclerotic plaques (n = 24) and in non-atherosclerotic arteries (n = 6). Up-regulation of IDO and genes related to the IDO pathway was found to be pronounced in atherosclerotic plaques. Immunohistochemistry demonstrated IDO protein in the atheromatous core and co-distribution with monocyte-macrophages (CD68-positive cells). In gene-set enrichment analysis, the IDO pathway revealed a significant (false discovery rate (FDR) = 0.07) regulatory T cell, fork-head box protein 3 (FoxP3)-initiated CD28-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-inducible T cell co-stimulator (ICOS)-driven pathway leading to activation of IDO expression in antigen-presenting cells (APCs). Expression of these IDO pathway genes varied between 2.1- and 16.8-fold as compared to control tissues (P < 0.05 for all).ConclusionsIDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis offering new viable therapeutic targets for the development of antiatherogenic immunosuppressive therapies.

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