دورية أكاديمية
Fatty acid oxidation fuels natural killer cell responses against infection and cancer.
| العنوان: | Fatty acid oxidation fuels natural killer cell responses against infection and cancer. |
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| المؤلفون: | Sheppard S; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.; Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom., Srpan K; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Lin W; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Lee M; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Delconte RB; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Owyong M; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.; Immunology and Microbial Pathogenesis Program, Graduate School of Medical Sciences, Weill Cornell Medical College, New York, NY 10065., Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, Vlaams Instituut voor Biotechnologie and Department of Oncology, Leuven Cancer Institute, Katholieke Universiteit Leuven, Leuven 3000, Belgium., Davis DM; Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom., Xavier JB; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Hsu KC; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Sun JC; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.; Immunology and Microbial Pathogenesis Program, Graduate School of Medical Sciences, Weill Cornell Medical College, New York, NY 10065. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Mar 12; Vol. 121 (11), pp. e2319254121. Date of Electronic Publication: 2024 Mar 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Neoplasms* , Virus Diseases*, Humans ; Lipid Metabolism ; Killer Cells, Natural ; Fatty Acids |
| مستخلص: | 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 13 C 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. Competing Interests: Competing interests statement:The authors declare no competing interest. |
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| معلومات مُعتمدة: | R01 AI100874 United States AI NIAID NIH HHS; P30 CA008748 United States CA NCI NIH HHS; T32 AI134632 United States AI NIAID NIH HHS; R01 AI155558 United States AI NIAID NIH HHS; R01 AI130043 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: NK cells; T cells; cancer; metabolism; virus infection |
| المشرفين على المادة: | 0 (Fatty Acids) |
| تواريخ الأحداث: | Date Created: 20240305 Date Completed: 20240307 Latest Revision: 20240517 |
| رمز التحديث: | 20240517 |
| مُعرف محوري في PubMed: | PMC10945797 |
| DOI: | 10.1073/pnas.2319254121 |
| PMID: | 38442180 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.2319254121 |