The impact of obesity onset on intraepithelial lymphocyte homeostasis at different ages.

According to the Centers for Disease Control and Prevention, one in six children and adolescents in the United States are obese. The obesity epidemic is caused by chronic excess energy intake and low energy expenditure. This energy imbalance creates excess adipose tissue that produces systemic inflammation in the body. Obesity is detrimental to barrier tissues that protect the body from foreign pathogens and environmental stressors. This metabolic disease disrupts normal homeostasis within the epithelium, which then results in complications that include more severe inflammatory bowel disease. We have identified that as obesity progresses, T cell numbers are reduced within the epithelial layer of the intestine and proliferation of these immune cells in the tissue becomes dysfunctional. Interestingly enough, we show that these same T cells are partially restored in number with a low-fat diet. We examined the relationship between obesity onset and the ability of intraepithelial lymphocytes to seed and proliferate in the intestine to maintain homeostasis in the barrier tissue. Here we demonstrate that obesity is particularly devastating in young mice that are still establishing lymphocyte populations in their epithelia. In addition, the long-term effects of chronic obesity from childhood to adulthood shows a dramatic reduction in the number of intraepithelial lymphocytes in the intestine. This study helps shed light on how epithelial barrier maintenance differs in early versus late onset of obesity and will direct research to explore alternative approaches to restore intestinal intraepithelial T cells and promote optimal barrier integrity in obese patients.