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Publication : The ATP-exporting channel Pannexin 1 promotes CD8(+) T cell effector and memory responses.

First Author  Vardam-Kaur T Year  2024
Journal  iScience Volume  27
Issue  7 Pages  110290
PubMed ID  39045105 Mgi Jnum  J:354844
Mgi Id  MGI:7704758 Doi  10.1016/j.isci.2024.110290
Citation  Vardam-Kaur T, et al. (2024) The ATP-exporting channel Pannexin 1 promotes CD8(+) T cell effector and memory responses. iScience 27(7):110290
abstractText  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.
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