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Fatty acid oxidation fuels natural killer cell responses against infection and cancer
File(s)
Author(s)
Sheppard, Sam
Srpan, Katja
Lin, Wendy
Lee, Mariah
Delconte, Rebecca B
Type
Journal Article
Abstract
Natural killer (NK) cells are a vital part of the innate immune system capable of rapidly clearing mutated or infected cells from the body and promoting an immune response. Here, we find that NK cells activated by viral infection or tumor challenge increase uptake of fatty acids and their expression of carnitine palmitoyltransferase I (CPT1A), a critical enzyme for long-chain fatty acid oxidation. Using a mouse model with an NK cell-specific deletion of CPT1A, combined with stable 13C isotope tracing, we observe reduced mitochondrial function and fatty acid-derived aspartate production in CPT1A-deficient NK cells. Furthermore, CPT1A-deficient NK cells show reduced proliferation after viral infection and diminished protection against cancer due to impaired actin cytoskeleton rearrangement. Together, our findings highlight that fatty acid oxidation promotes NK cell metabolic resilience, processes that can be optimized in NK cell-based immunotherapies.
Date Issued
2024-03-12
Date Acceptance
2024-01-25
Citation
Proceedings of the National Academy of Sciences of USA, 2024, 121 (11)
URI
URL
DOI
ISSN
0027-8424
Publisher
National Academy of Sciences
Journal / Book Title
Proceedings of the National Academy of Sciences of USA
Volume
121
Issue
11
Copyright Statement
This article is a PNAS Direct Submission.
Copyright © 2024 the Author(s). Published by PNAS.
This article is distributed under Creative Commons
Attribution-NonCommercial-NoDerivatives License 4.0
(CC BY-NC-ND).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38442180
Subjects
Fatty Acids
Humans
Killer Cells, Natural
Lipid Metabolism
Neoplasms
Virus Diseases
cancer
metabolism
NK cells
T cells
virus infection
Publication Status
Published
Coverage Spatial
United States
Article Number
e2319254121
Date Publish Online
2024-03-05