The ATP-exporting channel Pannexin 1 promotes CD8+ T cell effector and memory responses
Year: 2024
Type: article
Abstract: Sensing of extracellular ATP (eATP) controls CD8 + T cell function. Their accumulation can occur through export by specialized molecules, such as the release channel Pannexin-1 (Panx1). Whether Panx1 controls CD8 + T cell immune responses in vivo , however, has not been previously addressed. Here, we report that T cell-specific Panx1 is needed for CD8 + T cell responses to viral infections and cancer. We found that CD8-specific Panx1 promotes both effector and memory CD8 + T cell responses. Panx1 favors initial effector CD8 + T cell activation through extracellular ATP (eATP) export and subsequent P2RX4 activation, which helps promote full effector differentiation through extracellular lactate accumulation and its subsequent recycling. In contrast, Panx1 promotes memory CD8 + T cell survival primarily through ATP export and subsequent P2RX7 engagement, leading to improved mitochondrial metabolism. In summary, Panx1-mediated eATP export regulates effector and memory CD8 + T cells through distinct purinergic receptors and different metabolic and signaling pathways.
Source: iScience
Institutions: Mayo Clinic in Arizona, University of Minnesota
Language: English
Subfield: Physiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Awards: Regulation of T cell responses by P2RX7, DEFINING THE FUNCTION OF EXTRACELLULAR ATP SENSING FOR MEMORY CD8+ T CELL GENERATION AND LONGEVITY, G4551415525, G8189407139, T Cell Homeostasis, Control of antiviral memory CD8+ T cell longevity by extracellular ATP sensing, Role of P2RX7 in making CD8+ T cells for tumor immunotherapy.
OpenAlex ID: W4399731906