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Published on: October 25, 2024
TH17 Cell Frequency in Peripheral Blood Is Elevated in Overweight Children without Chronic Inflammatory Diseases
Theresa Isabell Schindler1, Johanna-Josophina Wagner1,2, Sybelle Goedicke-Fritz1,3
1Children's Hospital, Philipps University, Marburg, Germany.
Insights
Childhood obesity is linked to higher T helper 17 (TH17) cell frequencies and increased expression of RORC and IL-17A mRNA. These findings suggest obesity independently influences TH17 immunity in children.
Area of Science:
- Immunology
- Pediatrics
- Obesity Research
Background:
- Childhood obesity prevalence has surged, correlating with chronic inflammatory diseases.
- Adipose tissue releases IL-6 and TNF-α, promoting T helper 17 (TH17) cell differentiation.
- TH17 cells are defined by RORC expression and IL-17A production; murine models show increased TH17 cells in obesity.
Purpose of the Study:
- To investigate the association between overweight status and TH17 cell frequency in children.
- To determine if overweight children exhibit elevated messenger RNA (mRNA) levels of IL-17A and RORC.
- To explore these associations in children without pre-existing chronic inflammatory conditions.
Main Methods:
- Peripheral blood samples were collected from 15 overweight and 50 non-overweight children.
- TH17 cells were quantified via flow cytometry using intracellular IL-17A staining after Ionomycin stimulation.
- RORC and IL-17A mRNA expression levels were measured using real-time PCR.
Main Results:
- Overweight children showed significantly higher TH17 cell frequencies (34.7% vs 25.4%, p=0.0023).
- TH17 cell frequency positively correlated with body mass index (r=0.42, p=0.0005).
- Relative mRNA expression of RORC (p=0.013) and IL-17A (p=0.014) was upregulated in overweight children.
Conclusions:
- Childhood obesity is an independent factor associated with elevated circulating TH17 cells.
- Higher RORC and IL-17A mRNA expression in overweight children may stem from adipose tissue's inflammatory activity.
- Future studies on TH17 immunity should account for overweight status, not just 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 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.
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. 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.
Results:
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.
Conclusion:
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.
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