Journal article

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, Stephen C Jameson

Nature | NATURE PUBLISHING GROUP | Published : 2018

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 requir..

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University of Melbourne Researchers

Grants

Awarded by NIH


Awarded by MN Partnership Infrastructure Award MNPIF


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by NATIONAL INSTITUTE ON DRUG ABUSE


Funding Acknowledgements

We thank the UMN Flow Cytometry Resource for cell sorting, C. Henzler (UMN Supercomputing Institute) for bioinformatics analysis, F. Zhou (UMN Characterization Facility) for transmission electron microscopy, M. Pierson for viral plaque assays, the NIH Tetramer Core for peptide/MHC tetramers, and A. Goldrath, S. Kaech, G. Shadel, R. Jones, E. Pearce, M. Jenkins, V. Vezys and members of the Jamequist laboratory and UMN Center for Immunology for discussions. The UMN Characterization Facility is a member of the NSF-funded Materials Research Facilities Network (https://www.mrfn.org) via the MRSEC program. This work was supported by NIH grants AI38903 and AI75168 (S.C.J.), CA157971 (A.K.), and MN Partnership Infrastructure Award MNPIF#16.09 (A.K.). H.B.d.S. was supported by a CNPq research fellowship from the Ministry of Science, Technology and Innovation of Brazil.