T H 17 Cell Frequency in Peripheral Blood Is Elevated in Overweight Children without Chronic Inflammatory Diseases.

Background: 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 _H 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 _H 17 cell frequencies. The aim of this study was to explore whether being overweight was associated with an elevated frequency of circulating T _H 17 cells or elevated messenger RNA (mRNA)-levels of IL-17A and RORC in children without chronic inflammatory diseases.
Methods: 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 _H 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.
Results: We found significantly elevated T _H cell frequencies in overweight children compared then on-overweight controls with 34.7 ± 1.5% of CD3 ⁺ CD4 ⁺ cells versus 25.4 ± 2.4% (mean ± SEM, p  = 0.0023), respectively. Moreover, T _H cell frequencies correlated positively with body mass index ( r  = 0.42, p  = 0.0005, respectively). The relative mRNA expression of RORC ( p  = 0.013) and IL-17A ( p  = 0.014) were upregulated in overweight compared to non-overweight children.
Conclusion: Childhood obesity is an independent factor that is associated with an elevated frequency of circulating T _H 17 cells and higher expression of RORC- and IL-17A-mRNA after in vitro stimulation with Ionomycin. This might be due to the inflammatory activity of the fat tissue. Studies on T _H 17 immunity should not only be adjusted for acute and chronic inflammatory diseases but also for overweight.