The ATP-exporting channel Pannexin 1 promotes CD8+ T cell effector and memory responses

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 r...

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Published iniScience Vol. 27; no. 7; p. 110290
Main Authors Vardam-Kaur, Trupti, Banuelos, Alma, Gabaldon-Parish, Maria, Macedo, Bruna Gois, Salgado, Caio Loureiro, Wanhainen, Kelsey Marie, Zhou, Maggie Hanqi, van Dijk, Sarah, Santiago-Carvalho, Igor, Beniwal, Angad S., Leff, Chloe L., Peng, Changwei, Tran, Nhan L., Jameson, Stephen C., Borges da Silva, Henrique
Format Journal Article
LanguageEnglish
Published Elsevier Inc 19.07.2024
Elsevier
Subjects
Biochemistry
Biological sciences
Immune response
Immune system
Immunology
Natural sciences
Biological sciences
Biochemistry
Immunology
Immune response
Natural sciences
Immune system
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Summary: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. [Display omitted] •The hemichannel Panx1 promotes in vivo effector and memory CD8+ T cell responses•Panx1 promotes effector CD8+ T cells via eATP and lactate extracellular accumulation•Panx1 promotes memory CD8+ T cell survival by eATP export and activation of AMPK Natural sciences; Biological sciences; Biochemistry; Immunology; Immune response; Immune system
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Present address: Biomedical Sciences Graduate Program, University of California, San Diego, CA 92093, USA
Present address: Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA
Present address: Omeros Corporation, Seattle, WA 98119, USA
These authors contributed equally
Present address: University of New Mexico, Albuquerque, NM 87131, USA
Lead contact
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.110290