mPGES-1-Mediated Production of PGE 2 and EP4 Receptor Sensing Regulate T Cell Colonic Inflammation.

PGE(2) is a lipid mediator of the initiation and resolution phases of inflammation, as well as a regulator of immune system responses to inflammatory events. PGE(2) is produced and sensed by T cells, and autocrine or paracrine PGE(2) can affect T cell phenotype and function. In this study, we use a T cell-dependent model of colitis to evaluate the role of PGE(2) on pathological outcome and T-cell phenotypes. CD4(+) T effector cells either deficient in mPGES-1 or the PGE(2) receptor EP4 are less colitogenic. Absence of T cell autocrine mPGES1-dependent PGE(2) reduces colitogenicity in association with an increase in CD4(+) ROR gamma t(+) cells in the lamina propria. In contrast, recipient mice deficient in mPGES-1 exhibit more severe colitis that corresponds with a reduced capacity to generate FoxP3(+) T cells, especially in mesenteric lymph nodes. Thus, our research defines how mPGES-1-driven production of PGE(2) by different cell types in distinct intestinal locations impacts T cell function during colitis. We conclude that PGE(2) has profound effects on T cell phenotype that are dependent on the microenvironment.