The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8+ T cells

Henrique Borges da Silva, Lalit K. Beura, Haiguang Wang, Eric A. Hanse, Reshma Gore, Milcah C. Scott, Daniel A. Walsh, Katharine E. Block, Raissa Fonseca, Yan Yan, Keli L. Hippen, Bruce R. Blazar, David Masopust, Ameeta Kelekar, Lucy Vulchanova, Kristin A. Hogquist and Stephen C. Jameson ()
Additional contact information
Henrique Borges da Silva: University of Minnesota
Lalit K. Beura: University of Minnesota
Haiguang Wang: University of Minnesota
Eric A. Hanse: University of Minnesota
Reshma Gore: University of Minnesota
Milcah C. Scott: University of Minnesota
Daniel A. Walsh: University of Minnesota
Katharine E. Block: University of Minnesota
Raissa Fonseca: University of Minnesota
Yan Yan: University of Minnesota
Keli L. Hippen: University of Minnesota
Bruce R. Blazar: University of Minnesota
David Masopust: University of Minnesota
Ameeta Kelekar: University of Minnesota
Lucy Vulchanova: University of Minnesota
Kristin A. Hogquist: University of Minnesota
Stephen C. Jameson: University of Minnesota

Nature, 2018, vol. 559, issue 7713, 264-268

Abstract: Abstract Extracellular ATP (eATP) is an ancient ‘danger signal’ used by eukaryotes to detect cellular damage1. In mice and humans, the release of eATP during inflammation or injury stimulates both innate immune activation and chronic pain through the purinergic receptor P2RX72–4. It is unclear, however, whether this pathway influences the generation of immunological memory, a hallmark of the adaptive immune system that constitutes the basis of vaccines and protective immunity against re-infection5,6. Here we show that P2RX7 is required for the establishment, maintenance and functionality of long-lived central and tissue-resident memory CD8+ T cell populations in mice. By contrast, P2RX7 is not required for the generation of short-lived effector CD8+ T cells. Mechanistically, P2RX7 promotes mitochondrial homeostasis and metabolic function in differentiating memory CD8+ T cells, at least in part by inducing AMP-activated protein kinase. Pharmacological inhibitors of P2RX7 provoked dysregulated metabolism and differentiation of activated mouse and human CD8+ T cells in vitro, and transient P2RX7 blockade in vivo ameliorated neuropathic pain but also compromised production of CD8+ memory T cells. These findings show that activation of P2RX7 by eATP provides a common currency that both alerts the nervous and immune system to tissue damage, and promotes the metabolic fitness and survival of the most durable and functionally relevant memory CD8+ T cell populations.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0282-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:559:y:2018:i:7713:d:10.1038_s41586-018-0282-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0282-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().