Background: Childhood obesity now represents a major public health concern. Being obese in childhood appears to increase the risk of severe obesity in adulthood. Obesity is associated with co-morbid conditions such as type 2 diabetes and cardiovascular disease. Underpinning obesity is a state of chronic sterile inflammation. Recently the invariant natural killer T (iNKT) cell, an innate T cell was shown to act as a metabolic regulator and altered by obesity both in adults and children.
Hypothesis: We hypothesised that other innate T cells populations (Mucosal associated invariant T (MAIT) cells and Vδ3 T cells are impacted by obesity in children resulting in loss of regulation and increased inflammation.
Methods: We investigated the frequency and function of MAIT and Vδ3 T cells in a cohort of obese children (mean age 12.8, mean BMI z-score 4) and compared to a non-obese cohort of children (mean age 12.4, mean BMI z-score 0.3) by multi-colour flow cytometry. We correlated immune parameters with BMI, insulin levels and age using graph pad prism.
Results: We show that in obese children MAIT cells are increased in frequency (4% vs 1.8%) and a greater proportion produce IL-17 (10% vs 2%) when compared to non-obese cohort. Furthermore, MAIT cells upregulated PD-1 expression a marker of late activation/exhaustion. Vδ3 T cells were reduced in frequency (0.7% vs 1.1%) in obese children and upon stimulation a greater proportion produced high levels of the regulatory cytokine IL-10 compared to non-obese cohort (20% vs 1%).
Conclusion/Interpretation: Immune dysregulation leads to increased inflammation. We show that MAIT cells; a population of immmunoregulatory cells are expanded in childhood obesity. These cells display an altered/exhausted phenotype with increased IL-17 production; a cytokine implicated in the pathogenesis of numerous diseases including cancer and autoimmunity. In contrast, Vδ3 T cells are depleted in obese children and produce increased levels of IL-10, suggesting a possible compensatory mechanism to the observed systemic inflammation. Collectively this data shows significant immune dysregulation in obese children.