ATAC sequencing of murine NK cells treated with PGE2

ATAC sequencing was used to determine the impact of PGE2 signaling on NK cell function. Our analysis revealed that PGE2 induces a dysfunctional program in NK cells characterized by the inability to produce cytokines and chemokines upon their activation. Mechanistically, this program is governed by epigenetic changes downstream of the PGE2 receptors EP2 and EP4. Overall design: Murine NK cells were isolated from spleens of C57BL/6J or GzmbCrePtger2-/-Ptger4fl/fl mice and cultured for 5 days in low doses of IL-2 and IL15:IL15Ra. In vitro cultured NK cells were treated for 5h with PGE2 (100ng/ml) or conditioned medium (CM) from PGE2-producing control BRAFV600E cells. To assess the transcriptional changes upon activation, NK cells were treated for 1h with PGE2 or CM from control BRAFV600E and stimulated for the last 4h through the activating receptor NK.1.1.