Image_1_mPGES-1-Mediated Production of PGE2 and EP4 Receptor Sensing Regulate T Cell Colonic Inflammation.TIF Damian Maseda Amrita Banerjee Elizabeth M. Johnson Mary Kay Washington Hyeyon Kim Ken S. Lau Leslie J. Crofford 10.3389/fimmu.2018.02954.s001 https://frontiersin.figshare.com/articles/figure/Image_1_mPGES-1-Mediated_Production_of_PGE2_and_EP4_Receptor_Sensing_Regulate_T_Cell_Colonic_Inflammation_TIF/7465295 <p>PGE<sub>2</sub> 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<sub>2</sub> is produced and sensed by T cells, and autocrine or paracrine PGE<sub>2</sub> 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<sub>2</sub> on pathological outcome and T-cell phenotypes. CD4<sup>+</sup> T effector cells either deficient in mPGES-1 or the PGE<sub>2</sub> receptor EP4 are less colitogenic. Absence of T cell autocrine mPGES1-dependent PGE<sub>2</sub> reduces colitogenicity in association with an increase in CD4<sup>+</sup>RORγt<sup>+</sup> 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<sup>+</sup> T cells, especially in mesenteric lymph nodes. Thus, our research defines how mPGES-1-driven production of PGE<sub>2</sub> by different cell types in distinct intestinal locations impacts T cell function during colitis. We conclude that PGE<sub>2</sub> has profound effects on T cell phenotype that are dependent on the microenvironment.</p> 2018-12-14 04:11:21 IBD–inflammatory bowel diseases T cell PGE2 colitis Th17 & Tregs cells inflammation immunomodulation Th17 activation Treg = regulatory T cell