Prostaglandin E2 controls the metabolic adaptation of T cells to the intestinal microenvironment
Villa, M.; Sanin, D. E.; Apostolova, P.; Corrado, M.; Kabat, A. M.; Cristinzio, C.; Regina, A.; Carrizo, G.; Rana, N.; Stanczak, M. A.; Baixauli, F.; Grzes, K. M.; Cupovic, J.; Solagna, F.; Hackl, A.; Globig, A.-M.; Haessler, F.; Puleston, D. J.; Kelly, B.; Cabezas-Wallscheid, N.; Hasselblatt, P.; Bengsch, B.; Zeiser, R.; Sagar, ; Buescher, J. M.; Pearce, E. J.; Pearce, E. L.
Show abstract
Immune cells must adapt to different environments during the course of an immune response. We studied the adaptation of CD8+ T cells to the intestinal microenvironment and how this process shapes their residency in the gut. CD8+ T cells progressively remodel their transcriptome and surface phenotype as they acquire gut residency, and downregulate expression of mitochondrial genes. Human and mouse gut-resident CD8+ T cells have reduced mitochondrial mass, but maintain a viable energy balance to sustain their function. We found that the intestinal microenvironment is rich in prostaglandin E2 (PGE2), which drives mitochondrial depolarization in CD8+ T cells. Consequently, these cells engage autophagy to clear depolarized mitochondria, and enhance glutathione synthesis to scavenge reactive oxygen species (ROS) that result from mitochondrial depolarization. Impairing PGE2 sensing promotes CD8+ T cell accumulation in the gut, while tampering with autophagy and glutathione negatively impacts the T cell population. Thus, a PGE2-autophagy-glutathione axis defines the metabolic adaptation of CD8+ T cells to the intestinal microenvironment, to ultimately influence the T cell pool.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Postnatal intestinal epithelial maturation by LSD1 controls the small intestinal immune cell composition independently from the microbiota 97%
- Single-cell profiling uncovers regulatory programs of pathogenic Th2 cells in allergic asthma 96%
- Mechanisms of Epigenomic and Functional Convergence Between Glucocorticoid and IL4-Driven Macrophage Programming 96%
Similar papers in this journal
- Terminal differentiation and persistence of effector regulatory T cells essential for the prevention of intestinal inflammation 97%
- Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis 97%
- Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity 97%
Similar papers in this journal
- c-Myc plays a key role in IFN-γ induced persistence of Chlamydia trachomatis 96%
- Phosphoglycerate mutase regulates Treg differentiation through control of serine synthesis and one-carbon metabolism 96%
- Secreted antigen A peptidoglycan hydrolase is essential for Enterococcus faecium cell separation and priming of immune checkpoint inhibitor cancer therapy 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.