Generation of Functional T-Regulatory Cells in Children with Metabolic Syndrome
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ORIGINAL ARTICLE
Generation of Functional T-Regulatory Cells in Children with Metabolic Syndrome Włodzimierz Łuczyn´ski • Natalia Wawrusiewicz-Kurylonek • El_zbieta Iłendo • Artur Bossowski • Barbara Głowin´ska-Olszewska Adam Kre˛towski • Anna Stasiak-Barmuta
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Received: 5 April 2012 / Accepted: 23 July 2012 / Published online: 7 October 2012 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2012
Abstract Recent research implies a role of decreased number and/or function of T-regulatory cells (Tregs) in low-grade inflammation associated with obesity and atherosclerosis. The enhancement of atheroprotective immunity by the expansion of Tregs could serve as a therapeutic strategy in obesity-related immunological disturbances. The aim of our study was an attempt to generate Treg cells in children with risk factors for the development of cardiovascular disease and to compare the results to those obtained in healthy subjects. The study group consisted of 30 children with metabolic syndrome (MS) and 30 controls. Conventional CD4?CD25- cells separated from the peripheral blood were converted into Treg cells with the use of CD3/ CD28 antibodies and interleukin (IL)-2/transforming growth factor (TGF)-b stimulation. The expression of critical Treg molecules and cytokines was assessed at mRNA and protein levels. The percentages of Treg cells in the peripheral blood were significantly lower in the
W. Łuczyn´ski (&) A. Bossowski B. Głowin´ska-Olszewska Department of Pediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University of Białystok, Waszyngtona 17, 15-274 Białystok, Poland e-mail: [email protected] N. Wawrusiewicz-Kurylonek A. Kre˛towski Department of Diabetology, Endocrinology and Internal Medicine, Medical University of Białystok, Białystok, Poland E. Iłendo Department of Cytogenetics, Medical University of Białystok, Białystok, Poland A. Stasiak-Barmuta Department of Clinical Immunology, Medical University of Białystok, Białystok, Poland
children with MS compared to the healthy subjects. After the culture with CD3/CD28 and IL-2/TGF-b we detected a significant increase in the expression of Tregs marker transcription factor FoxP3. The Tregs induced from the children with MS varied from the ones obtained in the controls in the expression of some molecules at mRNA level (e.g. IL-27, LGAL, KLF10 and NRP1) yet not in proliferation studies. For the first time, we have demonstrated the possibility of generating functional Treg cells in children with MS. The results of our study could be used in the design of therapeutic interventions in obesity associated immunologic disturbances. Keywords Children Immunology Metabolic syndrome Obesity Abbreviations FoxP3 Forkhead winged/helix transcription factor 3 IFN Interferon IL Interleukin iTreg Induced T-regulatory cell MS Metabolic syndrome RT-PCR Real-time polymerase chain reaction TGF Transforming growth factor Tregs T-regulatory cells
Introduction Overweight and obesity, defined as an excessive development of adi
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