Indoleamine 2,3-Dioxygenase (IDO) Enzyme Links Innate Immunity and Altered T-Cell Differentiation in Non-ST Segment Elevation Acute Coronary Syndrome.

Autor: Zara C; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. chiara.zara11@gmail.com., Severino A; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. annaseverino71@gmail.com., Flego D; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. davideflego@gmail.com., Ruggio A; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. aurelianoruggio@gmail.com., Pedicino D; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. danialla@gmail.com., Giglio AF; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. ada.giglio@gmail.com., Trotta F; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. fr.trotta@hotmail.it., Lucci C; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. claudia.lucci87@gmail.com., D'Amario D; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. domenico.damario@gmail.com., Vinci R; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. ramona.vinci@hotmail.it., Pisano E; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. eugenia.pisano@libero.it., La Rosa G; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. giulio.larosa90@gmail.com., Biasucci LM; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. lmbiasucci@virgilio.it., Crea F; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. filippo.crea@unicatt.it., Liuzzo G; Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, 8, 00168 Largo A. Gemelli, Italy. giovanna.liuzzo@gmail.com.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2017 Dec 26; Vol. 19 (1). Date of Electronic Publication: 2017 Dec 26.
DOI: 10.3390/ijms19010063
Abstrakt: Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs) play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs) from non-ST segment elevation myocardial infarction (NSTEMI) patients, stable angina (SA) patients and healthy controls (HC) by real-time quantitative polymerase chain reaction (RT-qPCR) before and after in vitro maturation with lipopolysaccharide (LPS). The amount of tryptophan catabolite; kynurenine; was evaluated in the culture supernatants of mature-MDDCs by ELISA assay. Autologous mixed lymphocyte reaction (MLR) between mature-MDDCs and naïve T-cells was carried out to study the differentiation towards T-helper 1 (Th1) and induced regulatory T-cells (iTreg). Analysis of IDO mRNA transcripts in mature-MDDCs revealed a significant reduction in cells isolated from NSTEMI (625.0 ± 128.2; mean ± SEM) as compared with those from SA (958.5 ± 218.3; p = 0.041) and from HC (1183.6 ± 231.6; p = 0.034). Furthermore; the concentration of kynurenine was lower in NSTEMI patients (2.78 ± 0.2) and SA (2.98 ± 0.25) as compared with HC (5.1 ± 0.69 ng/mL; p = 0.002 and p = 0.016; respectively). When IDO-competent mature-MDDCs were co-cultured with allogeneic naïve T-cells, the ratio between the percentage of generated Th1 and iTreg was higher in NSTEMI (4.4 ± 2.9) than in SA (1.8 ± 0.6; p = 0.056) and HC (0.9 ± 0.3; p = 0.008). In NSTEMI, the tolerogenic mechanism of the immune response related to IDO production by activated MDDCs is altered, supporting their role in T-cell dysregulation.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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