Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Villa, M; Sanin, DE; Apostolova, P; Corrado, M; Kabat, AM; Cristinzio, C; Regina, A; Carrizo, GE; Rana, N; Stanczak, MA; Baixauli, F; Grzes, KM; Cupovic, J; Solagna, F; Hackl, A; Globig, AM; Hässler, F; Puleston, DJ; Kelly, B; Cabezas-Wallscheid, N; Hasselblatt, P; Bengsch, B; Zeiser, R; Sagar; Buescher, JM; Pearce, EJ; Pearce, EL.
Prostaglandin E2 controls the metabolic adaptation of T cells to the intestinal microenvironment.
Nat Commun. 2024; 15(1): 451
Doi: 10.1038/s41467-024-44689-2
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- Abstract:
- 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 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 pool. 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.
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- Humans - administration & dosage
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- Genes, Mitochondrial - administration & dosage
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