Prostaglandin E2-mediated T cell suppression requires expression of hydroxyprostaglandin dehydrogenase in regulatory T cells.. Mus musculus

Prostaglandins are involved in maintaining tissue integrity under homeostatic conditions. However, in chronic inflammation and cancer prostaglandins have been linked to immune deviation including strong suppression of effector T-cell function. Yet, the molecular mechanisms underlyingimmunosuppression and the cell types involved are only purely understood. Here, we show for the first time that Treg cells are the critical cellular component exerting immunosuppressive effects in prostaglandin E2 (PGE2)-rich environments. Hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes PGE2 into immunosuppressive metabolites, is the critical molecular link between prostaglandin accumulation, increased Treg-cell function and avoidance of tissue destruction. Overall design: Conditional HPGD knockout mice were crossed to FOXP3-Cre-YFP mice and Treg and Tconv isolated from spleens of these mice were compared with Treg and Tconv cells from control animals.