Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Dr. Lisa Cameron

Abstract

The abundance of Th2 cells in both the airways and circulation associates with asthma severity. Activation of CRTh2 expressed by Th2 cells mediates production of Th2 cytokines and inhibits apoptosis. Glucocorticosteroid effects occur through suppression of Th2 cytokines and induction of apoptosis. However, recent evidence shows that the total daily dose of inhaled glucocorticosteroids was positively correlated with the percentage of circulating Th2 cells. As such, we chose to examine regulation of Th2 cells by glucocorticosteroids. We used CCRF-CEM cells as a Th2 cell model and in vitro differentiated primary Th2 cells to study the effect of dexamethasone. Low dose dexamethasone treatment reduced IL-13 but surprisingly increased CRTh2, while only high dose induced apoptosis. Interestingly, T cell activation reduced glucocorticosteroid receptor signaling genes FKBP5 and GR transcript levels. Our results suggest that glucocorticosteroids at insufficient doses to trigger apoptosis may sustain CRTh2+ Th2 cells and thereby maintain inflammation.


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