Cutting Edge: STAT4 promotes Bhlhe40 induction to drive protective IFN-γ from NK cells during viral infection Journal Article
| Authors: | Kim, H.; Abbasi, A.; Sharrock, J.; Santosa, E. K.; Sheppard, S.; Lau, C. M.; Edelson, B. T.; Sun, J. C. |
| Article Title: | Cutting Edge: STAT4 promotes Bhlhe40 induction to drive protective IFN-γ from NK cells during viral infection |
| Abstract: | NK cells represent a cellular component of the mammalian innate immune system, and they mount rapid responses against viral infection, including the secretion of the potent antiviral effector cytokine IFN-γ. Following mouse CMV infection, Bhlhe40 was the most highly induced transcription factor in NK cells among the basic helix-loop-helix family. Bhlhe40 upregulation in NK cells depended upon IL-12 and IL-18 signals, with the promoter of Bhlhe40 enriched for STAT4 and the permissive histone H3K4me3, and with STAT4-deficient NK cells showing an impairment of Bhlhe40 induction and diminished H3K4me3. Transcriptomic and protein analysis of Bhlhe40-deficient NK cells revealed a defect in IFN-γ production during mouse CMV infection, resulting in diminished protective immunity following viral challenge. Finally, we provide evidence that Bhlhe40 directly promotes IFN-γ by binding throughout the Ifng loci in activated NK cells. Thus, our study reveals how STAT4-mediated control of Bhlhe40 drives protective IFN-γ secretion by NK cells during viral infection. Copyright © 2023 by The American Association of Immunologists, Inc. |
| Keywords: | mouse; animal; metabolism; animals; mice; basic helix-loop-helix transcription factors; homeodomain proteins; cytokine; cytokines; gamma interferon; mammal; natural killer cell; killer cells, natural; interferon-gamma; homeodomain protein; mammals; cytomegalovirus infection; interleukin 12; basic helix loop helix transcription factor; interleukin-12; cytomegalovirus infections; stat4 protein; stat4 transcription factor; bhlhe40 protein, mouse |
| Journal Title: | Journal of Immunology |
| Volume: | 211 |
| Issue: | 10 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2023-11-15 |
| Start Page: | 1469 |
| End Page: | 1474 |
| Language: | English |
| DOI: | 10.4049/jimmunol.2300402 |
| PUBMED: | 37830760 |
| PROVIDER: | scopus |
| PMCID: | PMC10842983 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Joseph C. Sun -- Source: Scopus |
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