Control of nutrient uptake by IRF4 orchestrates innate immune memory Journal Article
| Authors: | Santosa, E. K.; Kim, H.; Rückert, T.; Le Luduec, J. B.; Abbasi, A. J.; Wingert, C. K.; Peters, L.; Frost, J. N.; Hsu, K. C.; Romagnani, C.; Sun, J. C. |
| Article Title: | Control of nutrient uptake by IRF4 orchestrates innate immune memory |
| Abstract: | Natural killer (NK) cells are innate cytotoxic lymphocytes with adaptive immune features, including antigen specificity, clonal expansion and memory. As such, NK cells share many transcriptional and epigenetic programs with their adaptive CD8+ T cell siblings. Various signals ranging from antigen, co-stimulation and proinflammatory cytokines are required for optimal NK cell responses in mice and humans during virus infection; however, the integration of these signals remains unclear. In this study, we identified that the transcription factor IRF4 integrates signals to coordinate the NK cell response during mouse cytomegalovirus infection. Loss of IRF4 was detrimental to the expansion and differentiation of virus-specific NK cells. This defect was partially attributed to the inability of IRF4-deficient NK cells to uptake nutrients required for survival and memory generation. Altogether, these data suggest that IRF4 is a signal integrator that acts as a secondary metabolic checkpoint to orchestrate the adaptive response of NK cells during viral infection. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; animal tissue; cell survival; animal experiment; animal model; genetic transcription; cell differentiation; immune response; natural killer cell; effector cell; upregulation; adaptive immunity; cell metabolism; cytomegalovirus infection; cell expansion; antiviral activity; interferon regulatory factor 4; murine cytomegalovirus; iron homeostasis; nutrient uptake; article; trained immunity |
| Journal Title: | Nature Immunology |
| Volume: | 24 |
| Issue: | 10 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-10-01 |
| Start Page: | 1685 |
| End Page: | 1697 |
| Language: | English |
| DOI: | 10.1038/s41590-023-01620-z |
| PUBMED: | 37697097 |
| PROVIDER: | scopus |
| PMCID: | PMC11098052 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Joseph Sun -- Source: Scopus |
