| First Author | Villa M | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 451 |
| PubMed ID | 38200005 | Mgi Jnum | J:350883 |
| Mgi Id | MGI:7575205 | Doi | 10.1038/s41467-024-44689-2 |
| Citation | Villa M, et al. (2024) Prostaglandin E(2) controls the metabolic adaptation of T cells to the intestinal microenvironment. Nat Commun 15(1):451 |
| abstractText | Immune cells must adapt to different environments during the course of an immune response. Here we study the adaptation of CD8(+) T cells to the intestinal microenvironment and how this process shapes the establishment of the CD8(+) T cell pool. CD8(+) T cells progressively remodel their transcriptome and surface phenotype as they enter the gut wall, and downregulate expression of mitochondrial genes. Human and mouse intestinal CD8(+) T cells have reduced mitochondrial mass, but maintain a viable energy balance to sustain their function. We find that the intestinal microenvironment is rich in prostaglandin E(2) (PGE(2)), 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 PGE(2) sensing promotes CD8(+) T cell accumulation in the gut, while tampering with autophagy and glutathione negatively impacts the T cell pool. Thus, a PGE(2)-autophagy-glutathione axis defines the metabolic adaptation of CD8(+) T cells to the intestinal microenvironment, to ultimately influence the T cell pool. |
