TGFβ down-regulates PGE2 receptor subtype 2 in differentiating naïve human CD4+ T cells, resulting in a lack of expression and function in Th17 cells (P6281)

Abstract

Abstract Prostaglandin E2 (PGE2) is an important component in inflammatory diseases. Recently, PGE2 has been recognized as playing a critical role in determining CD4+ T helper cell differentiation and expansion (Th1 and Th17, respectively). In order to better understand the role prostaglandins play in differentiated human T-helper cells we determined the expression of various PG receptors in in vitro differentiated human Th1, Th2, and Th17 cells. Surprisingly, we found that while Th1 and Th2 cells express all four PGE2 receptor subtypes, Th17 cells did not express EP2 subtype as determined by qPCR. Stimulation with specific EP receptor agonists confirmed that Th17 cells did not express a functional EP2 receptor. This is in contrast with mouse Th17 which do not show this phenotype. We further found that this down-regulation of EP2 in human Th17 cells was dependent on exposure to TGFβ, and was dose dependent. This is in contrast to TGFβ reported effects on other cell types and also in mouse CD4+ T cells. This finding could explain why differentiated Th17 cells expand in the presence of PGE2, as they down-regulate an important regulatory feedback loop through EP2. Additionally, our data suggests that PGE2 receptor expression and biology in T cells may not translate from rodents to humans.