Cutting Edge: Cooperative interferon regulatory factor network shapes the NK-cell antiviral response Journal Article
| Authors: | Santosa, E. K.; Zhang, J. M.; Sauter, J. C.; Owyong, M.; Sun, J. C. |
| Article Title: | Cutting Edge: Cooperative interferon regulatory factor network shapes the NK-cell antiviral response |
| Abstract: | Natural killer (NK) cells are innate lymphocytes that exhibit adaptive traits particularly evident during cytomegalovirus (CMV) infection. Following mouse CMV (MCMV) infection, NK cells upregulate the transcription factors IRF4 and IRF8, which are indispensable for their survival and proliferation upon viral infection. However, it is unclear whether these factors are expressed within the same individual cell and whether deficiency in one could be compensated by the other. In this study, we observed that a subset of NK cells co-express high levels of IRF4 and IRF8 in an NFκB-dependent manner. These IRF4HighIRF8High NK cells are specifically enriched for activated but immature cells with high proliferative potential during MCMV infection. Functionally, NK cells lacking both IRF4 and IRF8 develop normally, but experience a more severe expansion defect during virus exposure compared to NK cells deficient in a single factor. Thus, our study reveals a cooperative interplay between IRF4- and IRF8-dependent transcriptional networks in regulating NK-cell antiviral responses. © The Author(s) 2025. Published by Oxford University Press on behalf of The American Association of Immunologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please |
| Keywords: | genetics; mouse; animal; metabolism; animals; mice; mice, knockout; immunoglobulin enhancer binding protein; mice, inbred c57bl; c57bl mouse; immunology; nf-kappa b; natural killer cell; killer cells, natural; innate immunity; immunity, innate; gene regulatory network; knockout mouse; transcriptional regulation; interferon regulatory factors; gene regulatory networks; herpes virus infection; herpesviridae infections; natural killer cells; muromegalovirus; interferon consensus sequence binding protein; interferon regulatory factor; interferon regulatory factor-4; viral infection |
| Journal Title: | Journal of Immunology |
| Volume: | 214 |
| Issue: | 6 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2025-06-01 |
| Start Page: | 1141 |
| End Page: | 1146 |
| Language: | English |
| DOI: | 10.1093/jimmun/vkaf041 |
| PUBMED: | 40180328 |
| PROVIDER: | scopus |
| PMCID: | PMC12213180 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Joseph Sun -- Source: Scopus |
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