Metabolic differences between Th2 and Th17 cells in airway inflammation

Abstract

Abstract Asthma is an airway inflammatory disease that is mediated by T effector (Teff) cells, specifically Th2 and Th17 cells. As disease increases in severity, there is a shift towards a higher Th17 response. Treatment of asthmatic patients include the use of glucocorticoid (GC) steroids. These drugs are effective at controlling inflammation in mild cases but as disease severity increases towards neutrophilic disease there is resistance by Th17 cells to effects of the drugs. A key therapeutic objective is to identify either alternative treatments for asthma or targets that make Th17 cells more susceptible to GCs. Studies have shown cells which have increased glycolysis and oxidative phosphorylation are more resistant to the effects of GCs. In this study we show, that in the murine model of airway inflammation there are differences in the expression of metabolic proteins between Th2 and Th17 cells that are present in the lung. This has been seen in cells that have higher amounts glucose uptake. These results imply that the higher glucose utilization of Th17 cells and their metabolic flexibility may contribute to their resistance to the effects of GCs. We also show by CyTOF of PBMCs that individuals with asthma have increased expression of metabolic associated proteins compared to control individuals in their CD4 cells. These data support the metabolic shift observed in our in vitro studies.