Longevity & AgingNew Immune Checkpoint PTGIR Found to Drive CD8 T Cell Exhaustion via NRF2
Researchers at Van Andel Institute discovered that the prostacyclin receptor PTGIR acts as a novel immune checkpoint controlling CD8+ T cell exhaustion. Using mouse models of chronic viral infection and cancer, they showed that NRF2—the master antioxidant regulator—paradoxically accelerates terminal T cell exhaustion despite reducing oxidative stress, doing so by upregulating PTGIR. When PTGIR was silenced, CD8+ T cells maintained stronger effector function, produced more IFN-γ and granzymes, and resisted terminal exhaustion. PTGIR signaling impairs T cell metabolism and cytokine production while inducing transcriptional features of exhaustion. These findings reveal a new druggable axis—NRF2→PTGIR—that could complement existing immune checkpoint inhibitor therapies.
