Abstract
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 TH17 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 TH17 cell frequencies. The aim of this study was to explore whether being overweight was associated with an elevated frequency of circulating TH17 cells or elevated messenger RNA (mRNA)-levels of IL-17A and RORC in children without chronic inflammatory diseases. 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. TH17 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. We found significantly elevated TH 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, TH 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. Childhood obesity is an independent factor that is associated with an elevated frequency of circulating TH17 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 TH17 immunity should not only be adjusted for acute and chronic inflammatory diseases but also for overweight.
Highlights
Being overweight affects adults by causing chronic diseases including type 2 diabetes, arterial hypertension, or coronary heart disease, but is an increasingly widespread health issue in childhood [1, 2]
We observed that in the absence of acute or chronic inflammatory diseases, the frequency of circulating T helper 17 (TH17) cells was significantly increased in overweight children compared to non-overweight controls and there was a positive correlation between TH17 cell frequency and body mass index (BMI)
BMI and TH17 cell frequency apparently do not show a linear correlation, since we found no significant correlation between BMI and TH17 cells when analyzing overweight and non-overweight children separately
Summary
Being overweight affects adults by causing chronic diseases including type 2 diabetes, arterial hypertension, or coronary heart disease, but is an increasingly widespread health issue in childhood [1, 2]. Obesity is a risk factor for allergic diseases like bronchial asthma and for various autoimmune diseases [4, 5]. It contributes to a low-grade chronic inflammation with higher numbers of macrophages, mast cells, neutrophils, B- and T-cells in adipose tissue [6, 7], but the underlying pathogenesis and complex mutual interactions between immunity and metabolism are not yet completely understood. Fat tissue produces IL-6 and TNF-α, which are stimuli for TH17 cell differentiation These cells are characterized by expression of the transcription factor receptor-related orphan receptor C (RORC) and by IL-17A production. The aim of this study was to explore whether being overweight was associated with an elevated frequency of circulating TH17 cells or elevated messenger RNA (mRNA)-levels of IL-17A and RORC in children without chronic inflammatory diseases
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