AUTHOR=Schindler Theresa Isabell , Wagner Johanna-Josophina , Goedicke-Fritz Sybelle , Rogosch Tobias , Coccejus Verena , Laudenbach Verena , Nikolaizik Wilfried , Härtel Christoph , Maier Rolf Felix , Kerzel Sebastian , Zemlin Michael 

TITLE=TH17 Cell Frequency in Peripheral Blood Is Elevated in Overweight Children without Chronic Inflammatory Diseases

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01543

DOI=10.3389/fimmu.2017.01543

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>The prevalence of obesity has dramatically increased in children in the last few decades and is associated with chronic inflammatory diseases. Fat tissue produces IL-6 and TNF-α, which are stimuli for T<sub>H</sub>17 cell differentiation. These cells are characterized by expression of the transcription factor receptor-related orphan receptor C (RORC) and by IL-17A production. In murine models, obesity has been linked with elevated T<sub>H</sub>17 cell frequencies. The aim of this study was to explore whether being overweight was associated with an elevated frequency of circulating T<sub>H</sub>17 cells or elevated messenger RNA (mRNA)-levels of IL-17A and RORC in children without chronic inflammatory diseases.</p></sec><sec id="ST2"><title>Methods</title><p>We studied peripheral blood samples from 15 overweight and 50 non-overweight children without a history of autoimmune diseases, asthma, atopic dermatitis or allergic rhinoconjunctivitis. T<sub>H</sub>17 cells were quantified in Ionomycin stimulated peripheral blood mononuclear cells by flow cytometry using intracellular IL-17A staining. RORC- and IL-17A expressions were measured by real-time PCR.</p></sec><sec id="ST3"><title>Results</title><p>We found significantly elevated T<sub>H</sub> cell frequencies in overweight children compared then on-overweight controls with 34.7 ± 1.5% of CD3<sup>+</sup>CD4<sup>+</sup> cells versus 25.4 ± 2.4% (mean ± SEM, <italic>p</italic> = 0.0023), respectively. Moreover, T<sub>H</sub> cell frequencies correlated positively with body mass index (<italic>r</italic> = 0.42, <italic>p</italic> = 0.0005, respectively). The relative mRNA expression of RORC (<italic>p</italic> = 0.013) and IL-17A (<italic>p</italic> = 0.014) were upregulated in overweight compared to non-overweight children.</p></sec><sec id="ST4"><title>Conclusion</title><p>Childhood obesity is an independent factor that is associated with an elevated frequency of circulating T<sub>H</sub>17 cells and higher expression of RORC- and IL-17A-mRNA after <italic>in vitro</italic> stimulation with Ionomycin. This might be due to the inflammatory activity of the fat tissue. Studies on T<sub>H</sub>17 immunity should not only be adjusted for acute and chronic inflammatory diseases but also for overweight.</p></sec>