The Effects of Glucocorticoids on Th2 Cell Phenotype and Function
Abstract
T helper 2 (Th2) cells play a crucial role in type 2-high asthma. Glucocorticoids (GC) are the primary treatment for type 2-high asthma but their long-term impact on Th2 cells is unclear. Severe asthmatics receiving high-dose GC treatment still experience symptoms, which are associated with increased frequency of Th2-Th17 cells. We hypothesized that chronic GC treatment primes Th2 cells to transition to Th2-Th17 cells in the presence of Th17 differentiating cytokines (TGF-β/IL-21). Experiments revealed that Th2 cells can transition to Th2-Th17 cells that were more viable than Th2 cells in chronic GC. Th2-Th17 cells exposed to chronic GC produced less thioredoxin interacting protein (TXNIP) mRNA, an inhibitor of the antioxidant thioredoxin (TXN), and more ATP-binding cassette sub-family B member 1 (ABCB1) mRNA, a multi-drug resistance gene. These results indicate Th2-Th17 cells may be less susceptible to GC-induced apoptosis due to acquiring stronger antioxidant capacity and/or faster export of GC.